434 results on '"Mucosal Infection"'
Search Results
2. In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19
- Author
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Viraj Mane, Rikin Mehta, Nadine Alvarez, Vijeta Sharma, Steven Park, Alisa Fox, Claire DeCarlo, Xiaoqi Yang, David S. Perlin, and Rebecca L. R. Powell
- Subjects
Secretory IgA ,human milk ,mucosal infection ,SARS-CoV-2 ,COVID-19 ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
ABSTRACTImmunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosae, with secretory form (sIgA) being dominant and uniquely stable. sIgA is challenging to produce recombinantly but is naturally found in human milk, which could be considered a global resource for this biologic, justifying its development as a mucosal therapeutic. Presently, SARS-CoV-2 was utilized as a model mucosal pathogen, and methods were developed to efficiently extract human milk sIgA from donors who were naïve to SARS-CoV-2 or had recovered from infection that elicited high-titer anti-SARS-CoV-2 Spike sIgA in their milk (pooled to make LCTG-002). Mass spectrometry determined that proteins with a relative abundance of 1% or greater were all associated with sIgA. Western blot demonstrated that all batches consisted predominantly of sIgA. Compared to control IgA, LCTG-002 demonstrated significantly higher Spike binding (mean endpoint of 0.87 versus 5.87). LCTG-002 was capable of blocking the Spike receptor-binding domain – angiotensin-converting enzyme 2 (ACE2) interaction with significantly greater potency compared to control (mean LCTG-002 IC50 154ug/mL versus 50% inhibition not achieved for control), and exhibited significant neutralization activity against Spike-pseudotyped virus infection (mean LCTG-002 IC50 49.8ug/mL versus 114.5ug/mL for control). LCTG-002 was tested for its capacity to reduce viral lung burden in K18+hACE2 transgenic mice inoculated with SARS-CoV-2. LCTG-002 significantly reduced SARS-CoV-2 titers compared to control when administered at 0.25 mg/day or 1 mg/day, with a maximum TCID50 reduction of 4.9 logs. This innovative study demonstrates that LCTG-002 is highly pure and efficacious in vivo, supporting further development of milk-derived, polyclonal sIgA therapeutics.
- Published
- 2024
- Full Text
- View/download PDF
3. Disruption of IL-17-mediated immunosurveillance in the respiratory mucosa results in invasive Streptococcus pyogenes infection.
- Author
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Mills, Jamie-Lee, Lepletier, Ailin, Ozberk, Victoria, Dooley, Jessica, Kaden, Jacqualine, Calcutt, Ainslie, Yongbao Huo, Hicks, Allan, Zaid, Ali, Good, Michael F., and Pandey, Manisha
- Subjects
RESPIRATORY mucosa ,STREPTOCOCCUS pyogenes ,STREPTOCOCCAL diseases ,RHEUMATIC fever ,PHARYNGITIS ,GERMINAL centers ,BACTERIAL colonies - Abstract
Introduction: Streptococcus pyogenes is a Gram-positive pathogen that causes a significant global burden of skin pyoderma and pharyngitis. In some cases, infection can lead to severe invasive streptococcal diseases. Previous studies have shown that IL-17 deficiency in mice (IL-17
-/- ) can reduce S. pyogenes clearance from the mucosal surfaces. However, the effect of IL-17 on the development of severe invasive streptococcal disease has not yet been assessed. Methods: Here, we modeled single or repeated non-lethal intranasal (IN) S. pyogenes M1 strain infections in immunocompetent and IL-17-/- mice to assess bacterial colonization following a final IN or skin challenge. Results: Immunocompetent mice that received a single S. pyogenes infection showed long-lasting immunity to subsequent IN infection, and no bacteria were detected in the lymph nodes or spleens. However, in the absence of IL-17, a single IN infection resulted in dissemination of S. pyogenes to the lymphoid organs, which was accentuated by repeated IN infections. In contrast to what was observed in the respiratory mucosa, skin immunity did not correlate with the systemic levels of IL-17. Instead, it was found to be associated with the activation of germinal center responses and accumulation of neutrophils in the spleen. Discussion: Our results demonstrated that IL-17 plays a critical role in preventing invasive disease following S. pyogenes infection of the respiratory tract. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
4. Animal models of Klebsiella pneumoniae mucosal infections.
- Author
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Assoni, Lucas, Melo Couto, Ana Julia, Vieira, Brenda, Milani, Bárbara, Lima, Alice Souza, Converso, Thiago Rojas, and Darrieux, Michelle
- Subjects
KLEBSIELLA pneumoniae ,BRACHYDANIO ,ANIMAL models in research ,MUCOUS membranes ,GREATER wax moth ,DROSOPHILA melanogaster - Abstract
Klebsiella pneumoniae is among the most relevant pathogens worldwide, causing high morbidity and mortality, which is worsened by the increasing rates of antibiotic resistance. It is a constituent of the host microbiota of different mucosa, that can invade and cause infections in many different sites. The development of new treatments and prophylaxis against this pathogen rely on animal models to identify potential targets and evaluate the efficacy and possible side effects of therapeutic agents or vaccines. However, the validity of data generated is highly dependable on choosing models that can adequately reproduce the hallmarks of human diseases. The present review summarizes the current knowledge on animal models used to investigate K. pneumoniae infections, with a focus on mucosal sites. The advantages and limitations of each model are discussed and compared; the applications, extrapolations to human subjects and future modifications that can improve the current techniques are also presented. While mice are the most widely used species in K. pneumoniae animal studies, they present limitations such as the natural resistance to the pathogen and difficulties in reproducing the main steps of human mucosal infections. Other models, such as Drosophila melanogaster (fruit fly), Caenorhabditis elegans, Galleria mellonella and Danio rerio (zebrafish), contribute to understanding specific aspects of the infection process, such as bacterial lethality and colonization and innate immune system response, however, they but do not present the immunological complexity of mammals. In conclusion, the choice of the animal model of K. pneumoniae infection will depend mainly on the questions being addressed by the study, while a better understanding of the interplay between bacterial virulence factors and animal host responses will provide a deeper comprehension of the disease process and aid in the development of effective preventive/therapeutic strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Disruption of IL-17-mediated immunosurveillance in the respiratory mucosa results in invasive Streptococcus pyogenes infection
- Author
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Jamie-Lee Mills, Ailin Lepletier, Victoria Ozberk, Jessica Dooley, Jacqualine Kaden, Ainslie Calcutt, Yongbao Huo, Allan Hicks, Ali Zaid, Michael F. Good, and Manisha Pandey
- Subjects
S. pyogenes ,IL-17 ,invasive streptococcal infection ,mucosal infection ,natural immunity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionStreptococcus pyogenes is a Gram-positive pathogen that causes a significant global burden of skin pyoderma and pharyngitis. In some cases, infection can lead to severe invasive streptococcal diseases. Previous studies have shown that IL-17 deficiency in mice (IL-17−/−) can reduce S. pyogenes clearance from the mucosal surfaces. However, the effect of IL-17 on the development of severe invasive streptococcal disease has not yet been assessed.MethodsHere, we modeled single or repeated non-lethal intranasal (IN) S. pyogenes M1 strain infections in immunocompetent and IL-17−/− mice to assess bacterial colonization following a final IN or skin challenge.ResultsImmunocompetent mice that received a single S. pyogenes infection showed long-lasting immunity to subsequent IN infection, and no bacteria were detected in the lymph nodes or spleens. However, in the absence of IL-17, a single IN infection resulted in dissemination of S. pyogenes to the lymphoid organs, which was accentuated by repeated IN infections. In contrast to what was observed in the respiratory mucosa, skin immunity did not correlate with the systemic levels of IL-17. Instead, it was found to be associated with the activation of germinal center responses and accumulation of neutrophils in the spleen.DiscussionOur results demonstrated that IL-17 plays a critical role in preventing invasive disease following S. pyogenes infection of the respiratory tract.
- Published
- 2024
- Full Text
- View/download PDF
6. Animal models of Klebsiella pneumoniae mucosal infections
- Author
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Lucas Assoni, Ana Julia Melo Couto, Brenda Vieira, Bárbara Milani, Alice Souza Lima, Thiago Rojas Converso, and Michelle Darrieux
- Subjects
Klebsiella pneumoniae ,animal models ,disease pathogenesis ,mucosal infection ,pre-clinical ,Microbiology ,QR1-502 - Abstract
Klebsiella pneumoniae is among the most relevant pathogens worldwide, causing high morbidity and mortality, which is worsened by the increasing rates of antibiotic resistance. It is a constituent of the host microbiota of different mucosa, that can invade and cause infections in many different sites. The development of new treatments and prophylaxis against this pathogen rely on animal models to identify potential targets and evaluate the efficacy and possible side effects of therapeutic agents or vaccines. However, the validity of data generated is highly dependable on choosing models that can adequately reproduce the hallmarks of human diseases. The present review summarizes the current knowledge on animal models used to investigate K. pneumoniae infections, with a focus on mucosal sites. The advantages and limitations of each model are discussed and compared; the applications, extrapolations to human subjects and future modifications that can improve the current techniques are also presented. While mice are the most widely used species in K. pneumoniae animal studies, they present limitations such as the natural resistance to the pathogen and difficulties in reproducing the main steps of human mucosal infections. Other models, such as Drosophila melanogaster (fruit fly), Caenorhabditis elegans, Galleria mellonella and Danio rerio (zebrafish), contribute to understanding specific aspects of the infection process, such as bacterial lethality and colonization and innate immune system response, however, they but do not present the immunological complexity of mammals. In conclusion, the choice of the animal model of K. pneumoniae infection will depend mainly on the questions being addressed by the study, while a better understanding of the interplay between bacterial virulence factors and animal host responses will provide a deeper comprehension of the disease process and aid in the development of effective preventive/therapeutic strategies.
- Published
- 2024
- Full Text
- View/download PDF
7. Extensive/Multidrug-Resistant Pneumococci Detected in Clinical Respiratory Tract Samples in Southern Sweden Are Closely Related to International Multidrug-Resistant Lineages.
- Author
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Yamba Yamba, Linda, Uddén, Fabian, Fuursted, Kurt, Ahl, Jonas, Slotved, Hans-Christian, and Riesbeck, Kristian
- Subjects
STREPTOCOCCUS pneumoniae ,SEROTYPES ,RESPIRATORY infections ,WHOLE genome sequencing ,MULTIDRUG resistance ,MOLECULAR epidemiology ,DRUG resistance in bacteria ,LINEAGE - Abstract
Background/Objective: The frequencies of non-susceptibility against common antibiotics among pneumococci vary greatly across the globe. When compared to other European countries antibiotic resistance against penicillin and macrolides has been uncommon in Sweden in recent years. Multidrug resistance (MDR) is, however, of high importance since relevant treatment options are scarce. The purpose of this study was to characterize the molecular epidemiology, presence of resistance genes and selected virulence genes of extensively drug-resistant (XDR) (n =15) and MDR (n =10) Streptococcus pneumoniae detected in clinical respiratory tract samples isolated from patients in a southern Swedish county 2016-2018. With the aim of relating them to global MDR pneumococci. Methods: Whole genome sequencing (WGS) was performed to determine molecular epidemiology, resistance genes and presence of selected virulence factors. Antimicrobial susceptibility profiles were determined using broth microdilution testing. Further analyses were performed on isolates from the study and from the European nucleotide archive belonging to global pneumococcal sequence cluster (GPSC) 1 (n= 86), GPSC9 (n= 55) and GPSC10 (n= 57). Bacteria were analyzed regarding selected virulence determinants (pilus islet 1, pilus islet 2 and Zinc metalloproteinase C) and resistance genes. Results: Nineteen of 25 isolates were related to dominant global MDR lineages. Seventeen belonged to GPSC1, GPSC9 or GPSC10 with MDR non-PCV serotypes in GPSC9 (serotype 15A and 15C) as well as GPSC10 (serotype 7B, 15B and serogroup 24). Pilus islet-1 and pilus islet-2 were present in most sequence types belonging to GPSC1 and in two isolates within GPSC9 but were not detected in isolates belonging to GPSC10. Zinc metalloproteinase C was well conserved within all analyzed isolates belonging to GPSC9 but were not found in isolates from GPSC1 or GPSC10. Conclusions: Although MDR S. pneumoniae is relatively uncommon in Sweden compared to other countries, virulent non-PCV serotypes that are MDR may become an increasing problem, particularly from clusters GPSC9 and GPSC10. Since the incidence of certain serotypes (3, 15A, and 19A) found among our MDR Swedish study isolates are persistent or increasing in invasive pneumococcal disease further surveillance is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. Extensive/Multidrug-Resistant Pneumococci Detected in Clinical Respiratory Tract Samples in Southern Sweden Are Closely Related to International Multidrug-Resistant Lineages
- Author
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Linda Yamba Yamba, Fabian Uddén, Kurt Fuursted, Jonas Ahl, Hans-Christian Slotved, and Kristian Riesbeck
- Subjects
antimicrobial resistance (AMR) ,extensive drug resistance (XDR) ,multidrug-resistant (MDR) ,global pneumococcal sequence cluster ,mucosal infection ,respiratory tract ,Microbiology ,QR1-502 - Abstract
Background/ObjectiveThe frequencies of non-susceptibility against common antibiotics among pneumococci vary greatly across the globe. When compared to other European countries antibiotic resistance against penicillin and macrolides has been uncommon in Sweden in recent years. Multidrug resistance (MDR) is, however, of high importance since relevant treatment options are scarce. The purpose of this study was to characterize the molecular epidemiology, presence of resistance genes and selected virulence genes of extensively drug-resistant (XDR) (n=15) and MDR (n=10) Streptococcus pneumoniae detected in clinical respiratory tract samples isolated from patients in a southern Swedish county 2016-2018. With the aim of relating them to global MDR pneumococci.MethodsWhole genome sequencing (WGS) was performed to determine molecular epidemiology, resistance genes and presence of selected virulence factors. Antimicrobial susceptibility profiles were determined using broth microdilution testing. Further analyses were performed on isolates from the study and from the European nucleotide archive belonging to global pneumococcal sequence cluster (GPSC) 1 (n=86), GPSC9 (n=55) and GPSC10 (n=57). Bacteria were analyzed regarding selected virulence determinants (pilus islet 1, pilus islet 2 and Zinc metalloproteinase C) and resistance genes.ResultsNineteen of 25 isolates were related to dominant global MDR lineages. Seventeen belonged to GPSC1, GPSC9 or GPSC10 with MDR non-PCV serotypes in GPSC9 (serotype 15A and 15C) as well as GPSC10 (serotype 7B, 15B and serogroup 24). Pilus islet-1 and pilus islet-2 were present in most sequence types belonging to GPSC1 and in two isolates within GPSC9 but were not detected in isolates belonging to GPSC10. Zinc metalloproteinase C was well conserved within all analyzed isolates belonging to GPSC9 but were not found in isolates from GPSC1 or GPSC10.ConclusionsAlthough MDR S. pneumoniae is relatively uncommon in Sweden compared to other countries, virulent non-PCV serotypes that are MDR may become an increasing problem, particularly from clusters GPSC9 and GPSC10. Since the incidence of certain serotypes (3, 15A, and 19A) found among our MDR Swedish study isolates are persistent or increasing in invasive pneumococcal disease further surveillance is warranted.
- Published
- 2022
- Full Text
- View/download PDF
9. In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19.
- Author
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Mane V, Mehta R, Alvarez N, Sharma V, Park S, Fox A, DeCarlo C, Yang X, Perlin DS, and Powell RLR
- Subjects
- Humans, Mice, Animals, Milk, Human, Immunoglobulin A, Secretory, Disease Models, Animal, Immunoglobulin A, Mice, Transgenic, Antiviral Agents, SARS-CoV-2, COVID-19
- Abstract
Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosae, with secretory form (sIgA) being dominant and uniquely stable. sIgA is challenging to produce recombinantly but is naturally found in human milk, which could be considered a global resource for this biologic, justifying its development as a mucosal therapeutic. Presently, SARS-CoV-2 was utilized as a model mucosal pathogen, and methods were developed to efficiently extract human milk sIgA from donors who were naïve to SARS-CoV-2 or had recovered from infection that elicited high-titer anti-SARS-CoV-2 Spike sIgA in their milk (pooled to make LCTG-002). Mass spectrometry determined that proteins with a relative abundance of 1% or greater were all associated with sIgA. Western blot demonstrated that all batches consisted predominantly of sIgA. Compared to control IgA, LCTG-002 demonstrated significantly higher Spike binding (mean endpoint of 0.87 versus 5.87). LCTG-002 was capable of blocking the Spike receptor-binding domain - angiotensin-converting enzyme 2 (ACE2) interaction with significantly greater potency compared to control (mean LCTG-002 IC50 154ug/mL versus 50% inhibition not achieved for control), and exhibited significant neutralization activity against Spike-pseudotyped virus infection (mean LCTG-002 IC50 49.8ug/mL versus 114.5ug/mL for control). LCTG-002 was tested for its capacity to reduce viral lung burden in K18+hACE2 transgenic mice inoculated with SARS-CoV-2. LCTG-002 significantly reduced SARS-CoV-2 titers compared to control when administered at 0.25 mg/day or 1 mg/day, with a maximum TCID50 reduction of 4.9 logs. This innovative study demonstrates that LCTG-002 is highly pure and efficacious in vivo, supporting further development of milk-derived, polyclonal sIgA therapeutics.
- Published
- 2024
- Full Text
- View/download PDF
10. Bladder Morphology Using 2 Different Catheter Designs
- Author
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Cystosure, Innovative Research Inc., and Lennox Hoyte, MD, Principal Investigator
- Published
- 2017
11. Advances in Humanized Mouse Models to Improve Understanding of HIV-1 Pathogenesis and Immune Responses
- Author
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Amy Gillgrass, Jocelyn M. Wessels, Jack X. Yang, and Charu Kaushic
- Subjects
HIV-1 ,humanized mouse ,pathogenesis ,immune response ,mucosal infection ,microbiota ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Although antiretroviral therapy has transformed human immunodeficiency virus-type 1 (HIV-1) from a deadly infection into a chronic disease, it does not clear the viral reservoir, leaving HIV-1 as an uncurable infection. Currently, 1.2 million new HIV-1 infections occur globally each year, with little decrease over many years. Therefore, additional research is required to advance the current state of HIV management, find potential therapeutic strategies, and further understand the mechanisms of HIV pathogenesis and prevention strategies. Non-human primates (NHP) have been used extensively in HIV research and have provided critical advances within the field, but there are several issues that limit their use. Humanized mouse (Hu-mouse) models, or immunodeficient mice engrafted with human immune cells and/or tissues, provide a cost-effective and practical approach to create models for HIV research. Hu-mice closely parallel multiple aspects of human HIV infection and disease progression. Here, we highlight how innovations in Hu-mouse models have advanced HIV-1 research in the past decade. We discuss the effect of different background strains of mice, of modifications on the reconstitution of the immune cells, and the pros and cons of different human cells and/or tissue engraftment methods, on the ability to examine HIV-1 infection and immune response. Finally, we consider the newest advances in the Hu-mouse models and their potential to advance research in emerging areas of mucosal infections, understand the role of microbiota and the complex issues in HIV-TB co-infection. These innovations in Hu-mouse models hold the potential to significantly enhance mechanistic research to develop novel strategies for HIV prevention and therapeutics.
- Published
- 2021
- Full Text
- View/download PDF
12. Advancing Understanding of HIV Infection in Women Through Mucosal Immunology Studies
- Author
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Passmore, Jo-Ann S., Liebenberg, Lenine L., Mkhize, Nonhlanhla N., Archary, Derseree, Masson, Lindi, Abdool Karim, Quarraisha, editor, Abdool Karim, Salim S., editor, and Baxter, Cheryl, editor
- Published
- 2017
- Full Text
- View/download PDF
13. Advances in Humanized Mouse Models to Improve Understanding of HIV-1 Pathogenesis and Immune Responses.
- Author
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Gillgrass, Amy, Wessels, Jocelyn M., Yang, Jack X., and Kaushic, Charu
- Subjects
HIV ,HIV infections ,IMMUNE response ,HIV prevention ,MIXED infections ,IMMUNE reconstitution inflammatory syndrome - Abstract
Although antiretroviral therapy has transformed human immunodeficiency virus-type 1 (HIV-1) from a deadly infection into a chronic disease, it does not clear the viral reservoir, leaving HIV-1 as an uncurable infection. Currently, 1.2 million new HIV-1 infections occur globally each year, with little decrease over many years. Therefore, additional research is required to advance the current state of HIV management, find potential therapeutic strategies, and further understand the mechanisms of HIV pathogenesis and prevention strategies. Non-human primates (NHP) have been used extensively in HIV research and have provided critical advances within the field, but there are several issues that limit their use. Humanized mouse (Hu-mouse) models, or immunodeficient mice engrafted with human immune cells and/or tissues, provide a cost-effective and practical approach to create models for HIV research. Hu-mice closely parallel multiple aspects of human HIV infection and disease progression. Here, we highlight how innovations in Hu-mouse models have advanced HIV-1 research in the past decade. We discuss the effect of different background strains of mice, of modifications on the reconstitution of the immune cells, and the pros and cons of different human cells and/or tissue engraftment methods, on the ability to examine HIV-1 infection and immune response. Finally, we consider the newest advances in the Hu-mouse models and their potential to advance research in emerging areas of mucosal infections, understand the role of microbiota and the complex issues in HIV-TB co-infection. These innovations in Hu-mouse models hold the potential to significantly enhance mechanistic research to develop novel strategies for HIV prevention and therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
14. M cell-dependent antigen uptake on follicle-associated epithelium for mucosal immune surveillance
- Author
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Yutaka Nakamura, Shunsuke Kimura, and Koji Hase
- Subjects
FAE ,M cell ,Mucosal immune surveillance ,Antigen uptake ,Mucosa-associated lymphoid tissue (MALT) ,Mucosal infection ,Pathology ,RB1-214 - Abstract
Abstract The follicle-associated epithelium (FAE) covering mucosa-associated lymphoid tissue is distinct from the villous epithelium in cellular composition and functions. Interleukin-22 binding protein (IL-22BP), provided by dendritic cells at the sub-epithelial dome region, inhibits the IL-22-mediated secretion of antimicrobial peptides by the FAE. The Notch signal from stromal cells underneath the FAE diminishes goblet cell differentiation. These events dampen the mucosal barrier functions to allow luminal microorganisms to readily gain access to the luminal surface of the FAE. Furthermore, receptor activator of nucleic factor-kappa B ligand (RANKL) from a certain stromal cell type induces differentiation into microfold (M) cells that specialize in antigen uptake in the mucosa. Microfold (M) cells play a key role in mucosal immune surveillance by actively transporting external antigens from the gut lumen to the lymphoid follicle. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. For example, GPI-anchored molecules (e.g., glycoprotein 2 (GP2) and cellular prion protein (PrPC)) and β1-integrin facilitate the transport of specific types of xenobiotics. The antigen transport by M cells initiates antigen-specific mucosal immune responses represented by the induction of secretory immunoglobulin A (S-IgA). Meanwhile, several invasive pathogens exploit M cells as a portal to establish a systemic infection. Recent findings have uncovered the molecular machinery of differentiation and functions of M cells.
- Published
- 2018
- Full Text
- View/download PDF
15. What Genetics Tells Us About the Pathogenesis of IgA Nephropathy: The Role of Immune Factors and Infection
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Yue-Miao Zhang, Xu-Jie Zhou, and Hong Zhang
- Subjects
genetic predisposition ,genome-wide association study ,IgA nephropathy ,mucosal infection ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, which is characterized by IgA1-containing immune-deposits in the glomerular mesangium. The epidemiologic observations of familial clustering as well as ethnic and regional discrepancies indicate a genetic component to IgAN. Large, international, genome-wide association studies have identified several susceptibility genes and loci for IgAN, many of which have been implicated in immune regulation and are shared with other autoimmune diseases. Notably, increasing numbers of genes involved in mucosal immunity have been detected; such genes may impact the susceptibility and progression of IgAN through interaction with environmental stimuli (especially infection). Here, we discuss the innate and adaptive immune mechanisms that drive protective immunity against pathogens. Our goal is to provide a representative overview of the synergistic roles between genetic predisposition and infection in IgAN pathogenesis. We anticipate that these results will provide potential therapeutic agents and advances in precision medicine.
- Published
- 2017
- Full Text
- View/download PDF
16. Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence
- Author
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Lu Yu, Valerie P O'Brien, Jonathan Livny, Denise Dorsey, Nirmalya Bandyopadhyay, Marco Colonna, Michael G Caparon, Elisha DO Roberson, Scott J Hultgren, and Thomas J Hannan
- Subjects
mucosal infection ,recurrent infection ,mucosal remodeling ,uropathogenic E. coli ,tumor necrosis factor alpha ,urinary tract infection ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice promoted clearance of bladder-colonizing bacteria via rapid recruitment of neutrophils and subsequent exfoliation of infected bladder cells. In contrast, sustained TNFɑ signaling in Sensitized mice prolonged damaging inflammation, worsening infection. This work reveals how TNFɑ signaling dynamics can be rewired by a prior infection to shape diverse susceptibilities to future mucosal infections.
- Published
- 2019
- Full Text
- View/download PDF
17. Helicobacter pylori VacA Targets Myeloid Cells in the Gastric Lamina Propria To Promote Peripherally Induced Regulatory T-Cell Differentiation and Persistent Infection
- Author
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Aleksandra Altobelli, Michael Bauer, Karelia Velez, Timothy L. Cover, and Anne Müller
- Subjects
T-cell immunity ,T cells ,dendritic cells ,host-cell interactions ,immunomodulation ,mucosal infection ,Microbiology ,QR1-502 - Abstract
ABSTRACT The gastric bacterium Helicobacter pylori causes a persistent infection that is directly responsible for gastric ulcers and gastric cancer in some patients and protective against allergic and other immunological disorders in others. The two outcomes of the Helicobacter-host interaction can be modeled in mice that are infected as immunocompetent adults and as neonates, respectively. Here, we have investigated the contribution of the Helicobacter immunomodulator VacA to H. pylori-specific local and systemic immune responses in both models. We found that neonatally infected mice are colonized at higher levels than mice infected as adults and fail to generate effector T-cell responses to the bacteria; rather, T-cell responses in neonatally infected mice are skewed toward Foxp3-positive (Foxp3+) regulatory T cells that are neuropilin negative and express RORγt. We found these peripherally induced regulatory T cells (pTregs) to be enriched, in a VacA-dependent manner, not only in the gastric mucosa but also in the lungs of infected mice. Pulmonary pTreg accumulation was observed in mice that have been infected neonatally with wild-type H. pylori but not in mice that have been infected as adults or mice infected with a VacA null mutant. Finally, we traced VacA to gastric lamina propria myeloid cells and show that it suppressed interleukin-23 (IL-23) expression by dendritic cells and induced IL-10 and TGF-β expression in macrophages. Taken together, the results are consistent with the idea that H. pylori creates a tolerogenic environment through its immunomodulator VacA, which skews T-cell responses toward Tregs, favors H. pylori persistence, and affects immunity at distant sites. IMPORTANCE Helicobacter pylori has coexisted with humans for at least 60.000 years and has evolved persistence strategies that allow it to evade host immunity and colonize its host for life. The VacA protein is expressed by all H. pylori strains and is required for high-level persistent infection in experimental mouse models. Here, we show that VacA targets myeloid cells in the gastric mucosa to create a tolerogenic environment that facilitates regulatory T-cell differentiation, while suppressing effector T-cell priming and functionality. Tregs that are induced in the periphery during H. pylori infection can be found not only in the stomach but also in the lungs of infected mice, where they are likely to affect immune responses to allergens.
- Published
- 2019
- Full Text
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18. Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition)
- Author
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Wei-Hong Wang, Shiyao Chen, Jianzhong Zhang, Wei-Fen Xie, Xing-Zhou Xia, Yuan Yuan, Yong Xie, Bing-Yong Zhang, Xiaohua Hou, Chengwei Tang, Jian-Qiu Sheng, Bo Jiang, Zhen-Yu Zhang, Yin Zhu, Chun-Hui Lan, Ying Han, Yan Li, Song-Ze Ding, Yi-Qi Du, Yan-Qing Li, Kaichun Wu, Jing-Tong Wang, Gui-Bin Yang, Ye Chen, Gui-Ying Zhang, Yinglei Miao, Hong Lu, Yunsheng Yang, Changqing Yang, Jiaming Qian, Jing-Yuan Fang, Xiu-Li Zuo, Jingnan Li, Bin Lyu, Nong-Hua Lyu, Guo-Xin Zhang, Fu-Lian Hu, Zhirong Zeng, Jian-Ming Xu, Yongzhan Nie, Mingzhou Guo, Hua-Hong Wang, Minhu Chen, Heng-Jun Gao, Hai-Xing Jiang, Xue-Hong Wang, Jun-Ping Wang, Li-Ya Zhou, Wei-Chang Chen, Hong Cheng, Jiang-Bin Wang, Zhao-Shen Li, Youming Li, Peng-Yuan Zheng, Jie Liu, Youyong Lu, and Fen Wang
- Subjects
Mainland China ,Adult ,medicine.medical_specialty ,China ,13C-urea breath test ,Consensus ,Adolescent ,Delphi Technique ,Delphi method ,Guidelines ,mucosal infection ,Helicobacter Infections ,Young Adult ,medicine ,Infection control ,Humans ,Grading (education) ,Child ,Disease burden ,Aged ,Family Health ,Infection Control ,biology ,Helicobacter pylori ,Transmission (medicine) ,business.industry ,gastric cancer ,Gastroenterology ,Infant ,Middle Aged ,biology.organism_classification ,Infectious disease (medical specialty) ,Family medicine ,Child, Preschool ,helicobacter pylori - gastritis ,business - Abstract
Objective Helicobacter pyloriinfection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-basedH. pyloriinfection control and management to reduce the related disease burden. Methods Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. Results Experts discussed and modified the original 23 statements on family-basedH. pyloriinfection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1)H. pyloriinfection and transmission among family members, (2) prevention and management ofH. pyloriinfection in children and elderly people within households, and (3) strategies for prevention and management ofH. pyloriinfection for family members. In addition to the ‘test-and-treat’ and ‘screen-and-treat’ strategies, this consensus also introduced a novel third ‘family-basedH. pyloriinfection control and management’ strategy to prevent its intrafamilial transmission and development of related diseases. Conclusion H. pyloriis transmissible from person to person, and among family members. A family-basedH. pyloriprevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.
- Published
- 2021
19. Secreted Candida Proteins: Pathogenicity and Host Immunity
- Author
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Naglik, Julian R., Hube, Bernhard, Ashbee, Ruth, editor, and Bignell, Elaine M., editor
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- 2010
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20. Identification of Candida albicans regulatory genes governing mucosal infection.
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Meir, Juliane, Hartmann, Elena, Eckstein, Marie‐Therese, Guiducci, Eva, Kirchner, Florian, Rosenwald, Andreas, LeibundGut‐Landmann, Salomé, and Pérez, J. Christian
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- *
CANDIDA albicans , *ORAL mucosa diseases , *IMMUNE response , *CELL proliferation , *FUNGAL colonies - Abstract
Abstract: The fungus Candida albicans thrives on a variety of human mucosae, yet the fungal determinants that contribute to fitness on these surfaces remain underexplored. Here, by screening a collection of C. albicans deletion strains in a mouse model of oral infection (oropharyngeal candidiasis), we identify several novel regulatory genes that modulate the fitness of the fungus in this locale. We investigate in detail the interplay between the host mucosa and one of the identified mutants and establish that the C. albicans transcription regulator CUP9 is a key determinant of mucosal colonisation. Deletion of cup9 resulted in the formation of more foci of colonisation and heightened persistence in infected tongues. Furthermore, the cup9 mutant produced longer and denser filaments in the oral mucosa without eliciting an enhanced local immune response. Consistent with its role in oral colonisation, we show that CUP9's top target of regulation is a major effector of Candida's adherence to buccal cells. Finally, we establish that CUP9 also governs the interplay of the fungus with vaginal epithelial cells and has a role in vaginal infections, another common mucosal disease associated with Candida. Thus, our findings reveal a mechanism whereby C. albicans can regulate proliferation on mucosal surfaces. [ABSTRACT FROM AUTHOR]
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- 2018
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21. Microbiota-produced indole metabolites disrupt mitochondrial function and inhibit Cryptosporidium parvum growth.
- Author
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Funkhouser-Jones, Lisa J., Xu, Rui, Wilke, Georgia, Fu, Yong, Schriefer, Lawrence A., Makimaa, Heyde, Rodgers, Rachel, Kennedy, Elizabeth A., VanDussen, Kelli L., Stappenbeck, Thaddeus S., Baldridge, Megan T., and Sibley, L. David
- Abstract
Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children in resource-poor settings. To explore microbial influences on susceptibility, we screened 85 microbiota-associated metabolites for their effects on Cryptosporidium parvum growth in vitro. We identify eight inhibitory metabolites in three main classes: secondary bile salts/acids, a vitamin B 6 precursor, and indoles. Growth restriction of C. parvum by indoles does not depend on the host aryl hydrocarbon receptor (AhR) pathway. Instead, treatment impairs host mitochondrial function and reduces total cellular ATP, as well as directly reducing the membrane potential in the parasite mitosome, a degenerate mitochondria. Oral administration of indoles, or reconstitution of the gut microbiota with indole-producing bacteria, delays life cycle progression of the parasite in vitro and reduces the severity of C. parvum infection in mice. Collectively, these findings indicate that microbiota metabolites impair mitochondrial function and contribute to colonization resistance to Cryptosporidium infection. [Display omitted] • The microbiota provides resistance to infection by the protozoan parasite Cryptosporidium • Indole metabolites produced by adult microbiota inhibit Cryptosporidium growth in vitro • Indoles inhibit oxidative phosphorylation and decrease ATP levels in host cells • Indoles also depolarize the mitosome in the parasite, thus likely inhibiting vital functions Funkhouser-Jones et al. show that metabolites produced by the microbiota inhibit growth of Cryptosporidium. Bacterially produced indoles impair energy production by host mitochondria and disrupt the membrane potential of the mitosome, a remnant parasite mitochondrion. These findings demonstrate the basis for resistance against enteric parasite infection provided by the microbiota. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Candida albicans CHK1 gene from two-component system is essential for its pathogenicity in oral candidiasis
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Yulong Niu, Lei Cheng, Yangyang Shi, Xingchen Ye, Yujie Zhou, Chengguang Zhu, Binyou Liao, Biao Ren, and Xuedong Zhou
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Mutant ,Virulence ,Applied Microbiology and Biotechnology ,Microbiology ,Fungal Proteins ,Mice ,03 medical and health sciences ,Candidiasis, Oral ,In vivo ,Candida albicans ,Animals ,Gene ,030304 developmental biology ,0303 health sciences ,biology ,030306 microbiology ,Candidiasis ,General Medicine ,biology.organism_classification ,In vitro ,Corpus albicans ,Mucosal Infection ,biological phenomena, cell phenomena, and immunity ,Biotechnology - Abstract
The roles of Candida albicans CHK1, a key gene from two-component system, in oral mucosal infection are not clear. This study evaluated the key roles of CHK1 gene in vitro and in vivo. The expression of CHK1 and its regulated virulence factors were tested during the oral epithelial cell infection. The production of lactate dehydrogenase, ROS, and IL-1α combined with the confocal and scanning electron microscope observation was employed to identify the capability of CHK1 in damaging the epithelial cells. Both immunocompetent and immunodeficient mice oropharyngeal infection models were involved to confirm the roles of CHK1 gene in vivo. The expression of CHK1 gene was significantly increased during the oral epithelial cell infection. The chk1Δ/Δ mutant failed to damage the epithelial cells or induce IL-α and ROS production. Interestingly, chk1Δ/Δ can also form the similar hyphae with WT and complementary strains. Accordingly, chk1Δ/Δ did not affect the adhesion and invasion rates of C. albicans to oral epithelial cells. However, chk1Δ/Δ significantly decreased the expression levels of the virulence factors, including ALS2, SAP6, and YWP1. The chk1Δ/Δ also failed to cause oral candidiasis in both immunocompetent and immunodeficient mice indicating that CHK1 gene from the two-component system is essential for the pathogenicity of C. albicans. KEY POINTS: • CHK1gene is essential for C. albicans in oral candidiasis • C. albicans without CHK1 gene can form "non-pathogenic" hyphae. • CHK1 gene regulates the virulence of C. albicans.
- Published
- 2021
23. Candida albicans Interactions with Mucosal Surfaces during Health and Disease
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Spyridoula-Angeliki Nikou, Nessim Kichik, Rhys Brown, Nicole O. Ponde, Jemima Ho, Julian R. Naglik, and Jonathan P. Richardson
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Candida albicans ,commensal ,pathogen ,fungus ,mucosal infection ,microbiota ,Medicine - Abstract
Flexible adaptation to the host environment is a critical trait that underpins the success of numerous microbes. The polymorphic fungus Candida albicans has evolved to persist in the numerous challenging niches of the human body. The interaction of C. albicans with a mucosal surface is an essential prerequisite for fungal colonisation and epitomises the complex interface between microbe and host. C. albicans exhibits numerous adaptations to a healthy host that permit commensal colonisation of mucosal surfaces without provoking an overt immune response that may lead to clearance. Conversely, fungal adaptation to impaired immune fitness at mucosal surfaces enables pathogenic infiltration into underlying tissues, often with devastating consequences. This review will summarise our current understanding of the complex interactions that occur between C. albicans and the mucosal surfaces of the human body.
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- 2019
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24. The ironclad truth: how in vivo transcriptomics and in vitro mechanistic studies shape our understanding of Neisseria gonorrhoeae gene regulation during mucosal infection.
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Moreau, Matthew R., Massari, Paola, and Genco, Caroline A.
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- *
NEISSERIA gonorrhoeae , *NEISSERIA , *SEXUALLY transmitted diseases , *GONORRHEA , *DRUG resistance in microorganisms - Abstract
Neisseria gonorrhoeae is one of the most prevalent sexually transmitted infections worldwide. This obligate human pathogen has been extensively studied in vitro, where bacterial factors that are known to contribute to gonococcal disease and their regulation are relatively well defined. However, these in vitro experimental conditions only loosely replicate the host specific environment encountered by the bacteria in vivo. We recently reported on the complete gonococcal transcriptome expressed during natural human mucosal infection using RNA-seq analysis. Gene transcripts expressed in vivo (in vivo expressed factors) included genes encoding antibiotic resistance determinants, and a large number of hypothetical genes. A comparison of the gonococcal transcriptome expressed in vivo with the corresponding strain grown in vitro identified sets of genes regulated by infection, including those regulated by iron and the transcriptional regulatory protein Fur. We highlight here the role of Fur and gonococcal-specific regulatory processes important for infection and pathogenicity. We have determined that the genes controlled by Fur follow the same expression pattern in vivo as described previously in vitro, confirming Fur's regulatory role during infection. Collectively, these studies provide new insights into how bacterial fitness and pathogenicity are modulated during human mucosal infection. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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25. Non-typeable Streptococcus pneumoniae infection in a medical center in Taiwan after wide use of pneumococcal conjugate vaccine
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Chyi-Liang Chen, Lin-Hui Su, Cheng-Hsun Chiu, Hsin-Hang Chen, Mei-Hua Hsu, Rajendra Prasad Janapatla, Hsin-Chieh Li, and Tsu-Lan Wu
- Subjects
Adult ,0301 basic medicine ,Microbiology (medical) ,Heptavalent Pneumococcal Conjugate Vaccine ,Adolescent ,Respiratory System ,030106 microbiology ,lcsh:QR1-502 ,Taiwan ,Microbial Sensitivity Tests ,medicine.disease_cause ,lcsh:Microbiology ,Pneumococcal Infections ,Pneumococcal conjugate vaccine ,Microbiology ,Moraxella catarrhalis ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Streptococcus pneumoniae ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,030212 general & internal medicine ,Serotyping ,Child ,Aged ,Vaccines, Conjugate ,General Immunology and Microbiology ,biology ,business.industry ,Sputum ,General Medicine ,Middle Aged ,biology.organism_classification ,Anti-Bacterial Agents ,Mucosal Infection ,Penicillin ,Infectious Diseases ,Staphylococcus aureus ,Child, Preschool ,Carrier State ,Ceftriaxone ,medicine.symptom ,business ,medicine.drug - Abstract
Background: Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Most of the infection could be prevented through immunization by vaccines containing capsular polysaccharides but some infection may be caused by unencapsulated strains. Methods: Clinical isolates of S. pneumoniae from January 2012 to December 2015 at Chang Gung Memorial Hospital, Taiwan. Serotyping by PCR method was performed. Clinical and laboratory information of patients infected by non-typeable pneumococci (NTP) were collected and analyzed. Results: During the study period, 39 NTP isolates were identified. Most (21 of 39, 53.9%) were collected from purulent upper respiratory tract secretion. Others were from corneal abscess, sputum, and one from blood of a newborn. We recorded a 3.6-fold increase in the rate of isolation from 1.4% in 2012 to 5.0% in 2015 (p = 0.063). Co-infection was found in 24 cases; the major co-infecting pathogens included non-typeable Hemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Most (39 of 40, 97.5%) of the isolates were susceptible to both penicillin and ceftriaxone. The dominant sequence type ST1106 and an emerging sequence type ST7502 were recognized. Conclusions: A gradual increase of NTP infection was found in northern Taiwan in the pneumococcal conjugate vaccine era. Non-typeable pneumococci can cause respiratory and ophthalmological mucosal infection. Invasive infection can occur in newborns or young infants. Most of the isolates remained susceptible to penicillin and ceftriaxone. Keywords: Non-typeable Streptococcus pneumoniae, Pneumococcal conjugate vaccine, Penicillin, Ceftriaxone
- Published
- 2020
26. Comparative proteomics analysis indicates that palmatine contributes to transepithelial migration by regulating cellular adhesion
- Author
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Wang Hui, Yang Feng, Yan Baoqi, Dong Shuwei, Xin Ruihua, He Jiongjie, Cui Dongan, Sun Yan, Zhang Shidong, and Yan Zuoting
- Subjects
Lipopolysaccharides ,Berberine Alkaloids ,Pharmaceutical Science ,Proteomics ,030226 pharmacology & pharmacy ,01 natural sciences ,cell adhesion molecules ,Endometrium ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,Drug Discovery ,Leukocytes ,heterocyclic compounds ,Cells, Cultured ,Cell adhesion molecule ,Goats ,Palmatine ,Biological activity ,General Medicine ,Cell biology ,Molecular Medicine ,Female ,medicine.symptom ,Research Article ,endocrine system ,Down-Regulation ,Inflammation ,RM1-950 ,Transepithelial Migration ,complex mixtures ,03 medical and health sciences ,proteomics ,Cell Adhesion ,medicine ,Animals ,Cell adhesion ,Pharmacology ,mucosal inflammation ,organic chemicals ,Transendothelial and Transepithelial Migration ,Correction ,Epithelial Cells ,0104 chemical sciences ,Mucosal Infection ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,chemistry ,Therapeutics. Pharmacology - Abstract
Context Palmatine, a biologically active isoquinoline alkaloid, possesses multiple pharmaceutical activities against mucosal infection and inflammation. Objective There are no reports about the influence of palmatine on uterine mucosal epithelial cells. Materials and methods We used proteomics to analyse differentially expressed proteins (DEPs) in goat endometrial epithelial cells (EECs) stimulated by lipopolysaccharide (LPS, 5 μg/mL, the dosage can induce inflammatory response, according to our previous study) for 12 h and then treated with palmatine (80 μg/mL) for 8 h; the dosage was selected based on MTT assay. The EECs without any treatment were used as controls. Every group was treated in triplicate. Results A total of 428 DEPs in LPS-stimulated group and 486 DEPs in the palmatine-treated group were identified. Functional annotation analysis showed that palmatine mainly regulated the protein expression of structural molecules involved in the response to stimuli. Pathway analysis showed that cell adhesion molecule (CaM) pathways were most significant enriched due to palmatine treatment. Junction adhesion molecule 1 (JAM1), nectin 1 (NECT1) and cadherin 5 (CDH5), which play important roles in the transepithelial migration (TEpM) of leukocytes, were significantly downregulated by palmatine. Meanwhile, other proteins essential to the maintenance of cell adhesion and those that facilitate leukocyte migration were upregulated after palmatine treatment. Discussion and conclusions: The results suggested that palmatine regulates the expression of CaMs to affect TEpM during uterine mucosal inflammation and provides novel insight to understanding and developing palmatine pharmacology. Palmatine is a promising drug for treatment of mucosal inflammation.
- Published
- 2020
27. Special Issue: Mucosal Fungal Infections
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Jonathan P. Richardson and Julian R. Naglik
- Subjects
mucosal infection ,fungus ,Aspergillus ,Candida ,Cryptococcus ,Mucorales ,mycobiome ,Biology (General) ,QH301-705.5 - Abstract
The past four decades have seen a staggering escalation in the number of invasive fungal infections worldwide.[...]
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- 2018
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28. Candida–Epithelial Interactions
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Jonathan P. Richardson, Jemima Ho, and Julian R. Naglik
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epithelial cell ,Candida ,fungus ,mucosal infection ,commensalism ,pathogenicity ,microbiota ,Biology (General) ,QH301-705.5 - Abstract
A plethora of intricate and dynamic molecular interactions occur between microbes and the epithelial cells that form the mucosal surfaces of the human body. Fungi, particularly species of Candida, are commensal members of our microbiota, continuously interacting with epithelial cells. Transient and localised perturbations to the mucosal environment can facilitate the overgrowth of fungi, causing infection. This minireview will examine the direct and indirect mechanisms by which Candida species and epithelial cells interact with each other, and explore the factors involved in the central processes of adhesion, invasion, and destruction of host mucosal surfaces.
- Published
- 2018
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29. Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo.
- Author
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Deruaz, Maud, Moldt, Brian, Le, Khoa M., Power, Karen A., Vrbanac, Vladimir D., Tanno, Serah, Ghebremichael, Musie S., Allen, Todd M., Tager, Andrew M., Burton, Dennis R., and Luster, Andrew D.
- Subjects
- *
HIV infections , *IMMUNE system , *IMMUNOGLOBULINS , *IMMUNIZATION , *LABORATORY mice , *HIV prevention , *ANIMALS , *BIOLOGICAL models , *IMMUNITY , *MICE , *VIRAL antibodies , *TREATMENT effectiveness - Abstract
Humanized mice reconstituted with a human immune system can be mucosally infected with human immunodeficiency virus (HIV), opening up the possibility of studying HIV transmission in a small-animal model. Here we report that passive immunization with the broadly neutralizing antibody b12 protected humanized mice against repetitive intravaginal infection in a dose-dependent manner. In addition, treatment with the antibody PGT126, which is more potent in vitro, was more efficacious in vivo and provided sterilizing protection. Our results demonstrate that humanized mice can be used as a small-animal model to study the efficacy and mechanism of broadly neutralizing antibody protection against HIV acquisition. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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30. Systemic immunodominant CD8 responses with an effector-like phenotype are induced by intravaginal immunization with attenuated HSV vectors expressing HIV Tat and mediate protection against HSV infection.
- Author
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Nicoli, Francesco, Gallerani, Eleonora, Skarlis, Charalampos, Sicurella, Mariaconcetta, Cafaro, Aurelio, Ensoli, Barbara, Caputo, Antonella, Marconi, Peggy C., and Gavioli, Riccardo
- Subjects
- *
TAT protein , *PHENOTYPES , *VAGINAL contraceptives , *IMMUNIZATION , *IMMUNE response - Abstract
Mucosal HSV infection remains a public health issue in developing and developed world. However, an effective vaccine is still missing, partly because of the incomplete knowledge of correlates of protection. In this study we have investigated the kinetics and quality of immunity elicited by an attenuated HSV1 vector expressing the immunomodulatory Tat protein of HIV-1 (HSV1-Tat). Animals were immunized by intravaginal (IVag) or intradermal (ID) route with HSV1-Tat or with a control HSV1 vector expressing the LacZ gene (HSV1-LacZ) and immune responses were characterized in different anatomical districts. IVag immunization with HSV1-Tat enhanced both expansion and memory phases of HSV-specific immunodominant CD8 responses at systemic, but not local, level and induced short- and long-term protection against mucosal challenge. Conversely, ID immunization with HSV1-Tat favored HSV-subdominant CD8 responses, which protected mice only at early time points after immunization. IVag immunization, in particular with HSV1-Tat, compared to ID immunization, induced the differentiation of CD8 + T lymphocytes into short-lived effector (SLEC) and effector memory (Tem) cells, generating more robust recall responses associated with increased control of virus replication. Notably, systemic SLEC and Tem contributed to generate protective local secondary responses, demonstrating their importance for mucosal control of HSV. Finally, IgG responses were observed mostly in IVag HSV1-Tat immunized animals, although seemed dispensable for protection, which occurred even in few IgG negative mice. Thus, HSV1 vectors expressing Tat induce protective anti-HSV1 immune responses. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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31. Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans
- Author
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Selene Mogavero, Stephanie Wisgott, Stefanie Allert, Nadja Jablonowski, Frank M. Sauer, Osama Elshafee, Thomas Krüger, Daniela Schulz, Julian R. Naglik, Olaf Kniemeyer, Sascha Brunke, Axel A. Brakhage, Edward Dolk, and Bernhard Hube
- Subjects
Virulence ,Hypha ,Immunology ,Hyphae ,Biology ,biology.organism_classification ,Microbiology ,Article ,Corpus albicans ,Mucosal Infection ,Cell biology ,Fungal Proteins ,Epithelial Damage ,Virology ,Candida albicans ,Humans ,Secretion ,Candidalysin - Abstract
The human pathogenic fungus Candida albicans is a frequent cause of mucosal infections. Although the ability to transition from the yeast to the hypha morphology is essential for virulence, hypha formation and host cell invasion per se are not sufficient for the induction of epithelial damage. Rather, the hypha-associated peptide toxin, candidalysin, a product of the Ece1 polyprotein, is the critical damaging factor. While synthetic, exogenously added candidalysin is sufficient to damage epithelial cells, the level of damage does not reach the same level as invading C. albicans hyphae. Therefore, we hypothesized that a combination of fungal attributes is required to deliver candidalysin to the invasion pocket to enable the full damaging potential of C. albicans during infection. Utilising a panel of C. albicans mutants with known virulence defects, we demonstrate that the full damage potential of C. albicans requires the coordinated delivery of candidalysin to the invasion pocket. This process requires appropriate epithelial adhesion, hyphal extension and invasion, high levels of ECE1 transcription, proper Ece1 processing and secretion of candidalysin. To confirm candidalysin delivery, we generated camelid V HHs (nanobodies) specific for candidalysin and demonstrate localization and accumulation of the toxin only in C. albicans-induced invasion pockets. In summary, a defined combination of virulence attributes and cellular processes is critical for delivering candidalysin to the invasion pocket to enable the full damage potential of C. albicans during mucosal infection. Take Aways: Candidalysin is a peptide toxin secreted by C. albicans causing epithelial damage. Candidalysin delivery to host cell membranes requires specific fungal attributes. Candidalysin accumulates in invasion pockets created by invasive hyphae. Camelid nanobodies enabled visualisation of candidalysin in the invasion pocket.
- Published
- 2021
32. Host defence and persistent human papillomavirus infection
- Author
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Margaret Stanley
- Subjects
Antigen Presentation ,Innate immune system ,Host Microbial Interactions ,Antigen processing ,T cell ,T-Lymphocytes ,Papillomavirus Infections ,Dendritic cell ,Dendritic Cells ,Biology ,Virus ,Mucosal Infection ,medicine.anatomical_structure ,Immune system ,Virology ,Immunology ,medicine ,Cytotoxic T cell ,Animals ,Humans ,Persistent Infection ,Papillomaviridae ,Immune Evasion - Abstract
The ability to establish long term persistent infection is a feature of human papillomaviruses. The available evidence is that this ability is a consequence of a complex local immune milieu whereby innate immune receptors and signalling pathway cascades are inhibited by HPV early proteins resulting in failure of dendritic cell maturation, antigen processing and presentation and activation of cytotoxic antigen specific T cell responses. The development of cutaneous and mucosal infection models with the mouse papillomavirus MmuPV1 and the access to multiple gene deficient strains is providing the frame work to dissect the mechanisms underlying these complex host virus interactions.
- Published
- 2021
33. The Interactions Between Candida albicans and Mucosal Immunity
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Yujie Zhou, Lei Cheng, Yu L. Lei, Biao Ren, and Xuedong Zhou
- Subjects
0301 basic medicine ,Microbiology (medical) ,biology ,Phagocytosis ,immune escape ,Virulence ,biology.organism_classification ,Microbiology ,Corpus albicans ,QR1-502 ,Mucosal Infection ,Immunosurveillance ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Candida albicans ,immune recognition ,immune cell ,Pathogen ,mucosa ,030215 immunology - Abstract
Mucosa protects the body against external pathogen invasion. However, pathogen colonies on the mucosa can invade the mucosa when the immunosurveillance is compromised, causing mucosal infection and subsequent diseases. Therefore, it is necessary to timely and effectively monitor and control pathogenic microorganisms through mucosal immunity.Candida albicansis the most prevalent fungi on the mucosa. TheC. albicanscolonies proliferate and increase their virulence, causing severe infectious diseases and even death, especially in immunocompromised patients. The normal host mucosal immune defense inhibits pathogenicC. albicansthrough stepwise processes, such as pathogen recognition, cytokine production, and immune cell phagocytosis. Herein, the current advances in the interactions betweenC. albicansand host mucosal immune defenses have been summarized to improve understanding on the immune mechanisms against fungal infections.
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- 2021
34. Rhinosporidiosis in the Americas: A Systematic Review of Native Cases
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Sara Penagos, Carlos Andrés Agudelo, Juan José Castro, Natalia Zapata, and Alicia Hidron
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Rhinosporidium seeberi ,medicine.medical_specialty ,South asia ,biology ,business.industry ,Articles ,medicine.disease ,biology.organism_classification ,Dermatology ,Rhinosporidiosis ,Mucosal Infection ,Geographic distribution ,Infectious Diseases ,Virology ,medicine ,Humans ,Parasitology ,Americas ,Symptom Assessment ,Surgical treatment ,Ocular disease ,business - Abstract
Rhinosporidiosis is a chronic mucosal infection caused by Rhinosporidium seeberi, an aquatic protistan parasite. It presents as nasal or ocular polypoidal or vascularized masses. It is endemic in tropical and subtropical areas, especially in South Asia; R. seeberi´s endemicity in the Americas is often overlooked. The objective of this study was to describe the demographic and clinical characteristics of patients with rhinosporidiosis in the Americas, its management, and patient outcomes. This study is a systematic review of cases of human rhinosporidiosis in the Americas reported in the literature from 1896 to February 28, 2019. This review screened 1,994 reports, of which 115 were eligible for further analysis. The selected reports described 286 cases of human rhinosporidiosis between 1896 and 2019. Cases were diagnosed in Brazil (32.2%), Colombia (24.4%), Paraguay (12.6%), and the United States (11.9%). The majority of the cases (91%) occurred in geographic areas with altitudes < 1,000 m above sea level and in areas with median temperatures ≥ 25°C (67.3%). Most of the patients presented nasal (65%) and ocular involvement (35%). Surgical treatment was provided for 99.6% of patients, but 19.8% of them recurred. This review describes the under-recognized geographic distribution and clinical presentation of rhinosporidiosis in the Americas and highlights clinical differences to cases in Asia, specifically in reference to a higher prevalence of ocular disease and higher relapse rates.
- Published
- 2021
35. CCL19 and CCL28 Assist Herpes Simplex Virus 2 Glycoprotein D To Induce Protective Systemic Immunity against Genital Viral Challenge
- Author
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Xinmeng Guan, Qinxue Hu, Siyi He, Yalan Liu, Ming Fu, Chang Li, Xu Deng, Kai Hu, Mudan Zhang, Yan Yan, Sukun Luo, Zifeng Zheng, Tao Du, Lina Tong, and Wei Jin
- Subjects
0301 basic medicine ,Cellular immunity ,Immunogen ,glycoprotein D ,viruses ,Herpesvirus 2, Human ,030106 microbiology ,Antibodies, Viral ,Microbiology ,DNA vaccination ,03 medical and health sciences ,Mice ,Immune system ,Antigen ,Adjuvants, Immunologic ,Viral Envelope Proteins ,CCL19 ,Medicine ,Animals ,Molecular Biology ,Immunity, Mucosal ,Mice, Inbred BALB C ,biology ,business.industry ,Vaccination ,Herpes Simplex Virus Vaccines ,HSV-2 ,QR1-502 ,Mucosal Infection ,030104 developmental biology ,CCL28 ,Chemokines, CC ,Immunology ,Vagina ,biology.protein ,mucosal immunity ,Chemokine CCL19 ,Female ,Antibody ,business ,Immunologic Memory ,Research Article - Abstract
An effective HSV-2 vaccine should induce antigen (Ag)-specific immune responses against viral mucosal infection. This study reveals that chemokine CCL19 or CCL28 enhanced HSV-2 glycoprotein D ectodomain (gD-306aa)-induced immune responses against vaginal virus challenge., Potent systemic immunity is important for recalled mucosal immune responses, but in the defense against mucosal viral infections, it usually remains low at mucosal sites. Based on our previous findings that enhanced immune responses can be achieved by immunization with an immunogen in combination with a molecular adjuvant, here we designed chemokine-antigen (Ag) fusion constructs (CCL19- or CCL28-herpes simplex virus 2 glycoprotein D [HSV-2 gD]). After intramuscular (i.m.) immunization with different DNA vaccines in a prime and boost strategy, BALB/c mice were challenged with a lethal dose of HSV-2 through the genital tract. Ag-specific immune responses and chemokine receptor-specific lymphocytes were analyzed to determine the effects of CCL19 and CCL28 in strengthening humoral and cellular immunity. Both CCL19 and CCL28 were efficient in inducing long-lasting HSV-2 gD-specific systemic immunity. Compared to CCL19, less CCL28 was required to elicit HSV-2 gD-specific serum IgA responses, Th1- and Th2-like responses of immunoglobulin (Ig) subclasses and cytokines, and CCR3+ T cell enrichment (>8.5-fold) in spleens. These findings together demonstrate that CCL28 tends to assist an immunogen to induce more potently protective immunity than CCL19. This work provides information for the application potential of a promising vaccination strategy against mucosal infections caused by HSV-2 and other sexually transmitted viruses. IMPORTANCE An effective HSV-2 vaccine should induce antigen (Ag)-specific immune responses against viral mucosal infection. This study reveals that chemokine CCL19 or CCL28 enhanced HSV-2 glycoprotein D ectodomain (gD-306aa)-induced immune responses against vaginal virus challenge. In addition to eliciting robust humoral immune responses, the chemokine-Ag fusion construct also induced Th1- and Th2-like immune responses characterized by the secretion of multiple Ig subclasses and cytokines that were able to be recalled after HSV-2 challenge, while CCL28 appeared to be more effective than CCL19 in promoting gD-elicited immune responses as well as the migration of T cells to secondary lymph tissues. Of importance, both CCL19 and CCL28 significantly facilitated gD to induce protective mucosal immune responses in the genital tract. The above-described findings together highlight the potential of CCL19 or CCL28 in combination with gD as a vaccination strategy to control HSV-2 infection.
- Published
- 2021
36. CD34T+ Humanized Mouse Model to Study Mucosal HIV-1 Transmission and Prevention
- Author
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Florian Klein, Daniela Weiland, Kathrin Held, Kanika Vanshylla, Christof Geldmacher, Kanika Jain, Ricarda Stumpf, Franziska Kleipass, Jan Münch, Berthold Grüttner, Henning Gruell, and Tabea M. Eser
- Subjects
0301 basic medicine ,T cell ,Immunology ,lcsh:Medicine ,Article ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Drug Discovery ,medicine ,Pharmacology (medical) ,Pharmacology ,biology ,business.industry ,mucosal HIV-1 prevention ,broadly neutralizing antibodies ,lcsh:R ,3. Good health ,Mucosal Infection ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Lymphatic system ,humanized mice ,Viral replication ,030220 oncology & carcinogenesis ,Cord blood ,Humanized mouse ,biology.protein ,Antibody ,business - Abstract
Humanized mice are critical for HIV-1 research, but humanized mice generated from cord blood are inefficient at mucosal HIV-1 transmission. Most mucosal HIV-1 transmission studies in mice require fetal tissue-engraftment, the use of which is highly restricted or prohibited. We present a fetal tissue-independent model called CD34T+ with enhanced human leukocyte levels in the blood and improved T cell homing to the gut-associated lymphoid tissue. CD34T+ mice are highly permissive to intra-rectal HIV-1 infection and also show normal env diversification in vivo despite high viral replication. Moreover, mucosal infection in CD34T+ mice can be prevented by infusion of broadly neutralizing antibodies. CD34T+ mice can be rapidly and easily generated using only cord blood cells and do not require any complicated surgical procedures for the humanization process. Therefore, CD34T+ mice provide a novel platform for mucosal HIV-1 transmission studies as well as rapid in vivo testing of novel prevention molecules against HIV-1.
- Published
- 2021
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37. Experimental models of vaginal candidiasis and inflammation.
- Author
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Vecchiarelli, Anna, Gabrielli, Elena, and Pericolini, Eva
- Published
- 2015
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38. Gastrointestinal mucosal damage in patients with COVID-19 undergoing endoscopy: an international multicentre study
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Avik Sarkar, Francesco Azzolini, James J. Farrell, Fabio Ciceri, Michiel Bronswijk, Francesco Buttitta, Stefano Angeletti, Per Alberto Testoni, Michel Kahaleh, Emilio Di Giulio, Amy Tyberg, Kofi Oppong, Franco Bazzoli, Emanuele Dilaghi, Serena Porcari, Carolina Tomba, Gabriele Capurso, Guido Costamagna, Salvatore Greco, Cesare Burti, Ioannis S. Papanikolaou, Aurelio Mauro, Fabiana Zingone, P. Fracasso, Julio Iglesias-Garcia, Paolo Giorgio Arcidiacono, Edi Viale, Maria Elena Riccioni, Haroon Shahid, Govind Nair, Edoardo Savarino, Ivo Boškoski, Giuseppe Vanella, Leonardo Henry Eusebi, Philip Roelandt, Jin Woo Gene Yoo, Patrizia Rovere-Querini, Lorella Fanti, Luigi Ricciardiello, Antonio Di Sabatino, Everson L.A. Artifon, Maria Chiara Petrone, Schalk Van der Merwe, R Alexander Speight, Lieven Pouillon, Andre Lino, Daniel De la Iglesia-García, Vanella, G., Capurso, G., Burti, C., Fanti, L., Ricciardiello, L., Souza Lino, A., Boskoski, I., Bronswijk, M., Tyberg, A., Krishna Kumar Nair, G., Angeleti, S., Mauro, A., Zingone, F., Oppong, K. W., De La Iglesia-Garcia, D., Pouillon, L., Papanikolaou, I. S., Fracasso, P., Ciceri, F., Rovere-Querini, P., Tomba, C., Viale, E., Eusebi, L. H., Riccioni, M. E., Van Der Merwe, S., Shahid, H., Sarkar, A., Yoo, J. W. G., Dilaghi, E., Speight, R. A., Azzolini, F., Buttitta, F., Porcari, S., Petrone, M. C., Iglesias-Garcia, J., Savarino, E. V., Di Sabatino, A., Di Giulio, E., Farrell, J. J., Kahaleh, M., Roelandt, P., Costamagna, G., De Almeida Artifon, E. L., Bazzoli, F., Testoni, P. A., Greco, S., Arcidiacono, P. G., Vanella, Giuseppe, Capurso, Gabriele, Burti, Cesare, Fanti, Lorella, Ricciardiello, Luigi, Souza Lino, Andre, Boskoski, Ivo, Bronswijk, Michiel, Tyberg, Amy, Krishna Kumar Nair, Govind, Angeleti, Stefano, Mauro, Aurelio, Zingone, Fabiana, Oppong, Kofi W., de la Iglesia-Garcia, Daniel, Pouillon, Lieven, Papanikolaou, Ioannis S., Fracasso, Pierluigi, Ciceri, Fabio, Rovere-Querini, Patrizia, Tomba, Carolina, Viale, Edi, Eusebi, Leonardo Henry, Riccioni, Maria Elena, van der Merwe, Schalk, Shahid, Haroon, Sarkar, Avik, Yoo, Jin Woo (Gene), Dilaghi, Emanuele, Speight, R. Alexander, Azzolini, Francesco, Buttitta, Francesco, Porcari, Serena, Petrone, Maria Chiara, Iglesias-Garcia, Julio, Savarino, Edoardo V., Di Sabatino, Antonio, Di Giulio, Emilio, Farrell, James J., Kahaleh, Michel, Roelandt, Philip, Costamagna, Guido, de Almeida Artifon, Everson Luiz, Bazzoli, Franco, Testoni, Per Alberto, Greco, Salvatore, and Arcidiacono, Paolo Giorgio
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covid-19 ,endoscopy ,gastrointestinal tract ,mucosal infection ,aged ,COVID-19 ,colitis, ischemic ,cross-sectional studies ,duodenum ,female ,gastric mucosa ,gastrointestinal hemorrhage ,humans ,male ,middle aged ,pandemics ,prospective studies ,risk factors ,SARS-CoV-2 ,stomach ulcer ,endoscopy, gastrointestinal ,Male ,Cross-sectional study ,colitis ,RC799-869 ,Gastroenterology ,Endoscopy, Gastrointestinal ,law.invention ,0302 clinical medicine ,law ,Risk Factors ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,medicine.diagnostic_test ,Diseases of the digestive system. Gastroenterology ,Middle Aged ,Intensive care unit ,Exact test ,medicine.anatomical_structure ,Cohort ,030211 gastroenterology & hepatology ,Female ,Gastrointestinal Hemorrhage ,Colitis, Ischemic ,medicine.medical_specialty ,Duodenum ,Settore MED/12 - GASTROENTEROLOGIA ,ischemic ,COVID-19, Endoscopy, pandemic, ischemic lesions ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Stomach Ulcer ,Colitis ,Pandemics ,Aged ,business.industry ,medicine.disease ,gastrointestinal ,Endoscopy ,Cross-Sectional Studies ,Gastric Mucosa ,business - Abstract
BackgroundAlthough evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported.AimsWe aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19.MethodsAll consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ2 or Fisher’s exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors.ResultsBetween February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58–74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69–86.87)) and presence of GI symptoms (OR=6.17 (1.13–33.67)) were independently associated with major abnormalities at multivariate analysis.ConclusionIn this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy.Trial registration numberClinicalTrial.gov (ID: NCT04318366).
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- 2021
39. Overview of Candida albicans and Human Papillomavirus (HPV) Infection Agents and their Biomolecular Mechanisms in Promoting Oral Cancer in Pediatric Patients
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Stefania Cantore, Angela Pia Cazzolla, Edoardo Brauner, Mariateresa Ambrosino, Annarita Malcangi, Ioannis Alexandros Charitos, Lucrezia Bottalico, Lorenzo Lo Muzio, Riccardo Nocini, Luigi Santacroce, Andrea Ballini, Mario Dioguardi, and Michele Di Cosola
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Review Article ,Candida Albicans, HPV, Oral Cancer, Paediatric patients ,carcinoma ,medicine.disease_cause ,uterine cervical neoplasms ,risk factors ,humans ,Candida albicans ,Cervical cancer ,child ,biology ,alphapapillomavirus ,HPV infection ,dysbiosis ,General Medicine ,Corpus albicans ,female ,Carcinoma, Squamous Cell ,squamous cell carcinoma of head and neck ,Medicine ,Oral Cancer ,carcinogenesis ,oropharyngeal neoplasms ,papillomavirus infections ,HPV ,General Biochemistry, Genetics and Molecular Biology ,head and neck neoplasms ,male ,adolescent ,candida albicans ,candidiasis ,carcinoma, squamous cell ,human papillomavirus 16 ,mouth mucosa ,mouth neoplasms ,papillomaviridae ,medicine ,Carcinoma ,Candida Albicans ,General Immunology and Microbiology ,squamous cell ,business.industry ,Cancer ,medicine.disease ,biology.organism_classification ,Mucosal Infection ,stomatognathic diseases ,Immunology ,Paediatric patients ,Carcinogenesis ,business - Abstract
Oral carcinoma represents one of the most common malignancies worldwide. Oral squamous cell carcinomas (OSCCs) account over 90% of all oral malignant tumors and are characterized by high mortality in the advanced stages. Early diagnosis is often a challenge for its ambiguous appearance in early stages. Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, particularly cervical cancer and oropharyngeal carcinomas. In addition, Candida albicans (C. albicans), which is the principal fungi involved in the oral cancer development, may induce carcinogenesis through several mechanisms, mainly promoting inflammation. Medical knowledge and research on adolescent/pediatric patients’ management and prevention are in continuous evolution. Besides, microbiota can play an important role in maintaining oral health and therefore all human health. The aim of this review is to evaluate epidemiological and pathophysiological characteristics of the several biochemical pathways involved during HPV and C. albicans infections in pediatric dentistry.
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- 2021
40. G Protein-Coupled Receptor 109A Maintains the Intestinal Integrity and Protects Against ETEC Mucosal Infection by Promoting IgA Secretion
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Yuhong Gong, Xinxin Jin, Boyu Yuan, Yantao Lv, Guangmou Yan, Mingming Liu, Changxin Xie, Juxiong Liu, Yimei Tang, Hongyan Gao, Yufeng Zhu, Yanhua Huang, and Wei Wang
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Male ,0301 basic medicine ,enterotoxigenic Escherichia coli ,lcsh:Immunologic diseases. Allergy ,Immunology ,medicine.disease_cause ,Receptors, G-Protein-Coupled ,Tight Junctions ,Microbiology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Enterotoxigenic Escherichia coli ,medicine ,Animals ,Immunology and Allergy ,Secretion ,sodium butyrate ,Intestinal Mucosa ,Receptor ,Escherichia coli Infections ,Original Research ,Tight junction ,Sodium butyrate ,epithelium barrier ,GPR109A ,Mucosal Infection ,Mice, Inbred C57BL ,Blot ,Intestinal Diseases ,030104 developmental biology ,Mechanism of action ,chemistry ,secretory IgA ,030220 oncology & carcinogenesis ,Immunoglobulin A, Secretory ,medicine.symptom ,lcsh:RC581-607 - Abstract
Several studies have reported an intricate link between the G protein-coupled receptor 109A (GPR109A) and intestinal health. Upon activation, induced by butyric acid and β-hydroxybutyric acid, GPR109A regulates the expression of tight junction proteins, exerts anti-inflammatory effects, and maintains the integrity of the intestinal barrier. However, its function and the mechanism of action in combating the infection caused by exogenous pathogenic microorganisms remain unclear. This study established an animal model of infection by oral enterotoxigenic Escherichia coli (ETEC) gavage to examine the underlying mechanism(s) and protective effects of GPR109A on the intestinal tract. Experimental GPR109A–/–and GPR109A+/+ mice were orally administered with 1 × 109 colony-forming units (CFUs) of ETEC, and changes in body weight were then observed. The colonization and translocation of ETEC in the intestine were detected by the plate counting method. The expression of tight junction proteins and the levels of inflammatory factors and secretory IgA (SIgA) in the intestine were detected by quantitative real-time polymerase chain reaction (q-PCR), western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The results demonstrated that GPR109A–/–mice were more susceptible to ETEC infection, showing more severe inflammatory reactions and intestinal damage. Moreover, the secretion of IgA in the intestinal tract of GPR109A+/+ mice was significantly increased after ETEC infection, whereas the IgA levels in GPR109A–/–mice did not change significantly. We added 5 g/L sodium butyrate to the drinking water of all mice. The GPR109A+/+ mice were protected against ETEC infection and no effect was observed in GPR109A–/–mice. Similarly, sodium butyrate increased the SIgA content in the gut of the GPR109A+/+ mice and no effect was observed in GPR109A–/–mice. In conclusion, activated GPR109A is effective against the colonization and translocation of ETEC in the gut and maintains the integrity of the intestinal barrier, possibly by promoting the secretion of intestinal IgA.
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- 2021
41. Th17 cells provide direct protective effects that limit stomach parasite burden following orogastric mucosal Trypanosoma cruzi infection
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Christopher S. Eickhoff, Chan Dh, Catherine W. Cai, Richard J. DiPaolo, Blase, Krystal A. Meza, Audette Re, Daniel F. Hoft, and Kevin A. Bockerstett
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Chagas disease ,NADPH oxidase ,biology ,Intracellular parasite ,medicine.medical_treatment ,Cell ,biology.organism_classification ,medicine.disease ,Mucosal Infection ,Microbiology ,medicine.anatomical_structure ,Cytokine ,biology.protein ,medicine ,Macrophage ,Trypanosoma cruzi - Abstract
Trypanosoma cruzi is the intracellular parasite of Chagas disease, a chronic condition characterized by cardiac and gastrointestinal morbidity. Protective immunity requires CD4+ T cells, and Th1 cells and IFN-γ are important players in host defense. More recently, Th17 cells and IL-17 have been shown to exert protective functions in systemic T. cruzi infection. However, it remains unclear whether Th17 cells and IL-17A protect against mucosal infection, which is an important cause of human outbreaks. We found that IL-17RA knock-out (KO) mice are highly susceptible to orogastric infection, indicating an important function for this cytokine in mucosal immunity to T. cruzi. To investigate the specific role of Th17 cells for mucosal immunity, we reconstituted RAG1 KO mice with T. cruzi-specific T cell receptor transgenic Th17 cells prior to orogastric T. cruzi challenges. We found that Th17 cells provided protection against gastric mucosal T. cruzi infection, indicated by significantly lower stomach parasite burdens. In vitro macrophage infection assays revealed that protection by Th17 cells is reversed with IL-17A neutralization or loss of macrophage NADPH oxidase activity. Consistent with this, in vivo, mice lacking functional NADPH oxidase were not protected by Th17 cell transfer. These data are the first report that Th17 cells protect against mucosal T. cruzi infection, and identify a novel protective mechanism involving the induction of NADPH oxidase activity in macrophages by IL-17A. These studies provide important insights for Chagas vaccine development, and more broadly, increase our understanding of the diverse roles of Th17 cells in host defense.
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- 2020
42. Successful treatment of chronic hyperplastic candidiasis with 5-aminolevulinic acid photodynamic therapy: A case report
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Bingjie Li, Pan Wei, Hong Hua, Xiaosheng Hu, and Xin fang
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Male ,Surgical resection ,medicine.medical_specialty ,Epithelial dysplasia ,medicine.medical_treatment ,Biophysics ,Photodynamic therapy ,Dermatology ,medicine.disease_cause ,Gastroenterology ,Refractory ,Candidiasis, Oral ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Photosensitizing Agents ,business.industry ,Mouth Mucosa ,Aminolevulinic Acid ,Middle Aged ,Mucosal Infection ,Photochemotherapy ,Oncology ,Quality of Life ,Chronic hyperplastic candidiasis ,Carcinogenesis ,business - Abstract
Chronic hyperplastic candidiasis (CHC) is a chronic oral mucosal infection caused by Candida. Refractory hyperplastic lesions may lead to epithelial dysplasia and carcinogenesis. Traditional surgical resection may cause irreversible damage and effect the patient's quality of life. This paper reports the case of a 63-year-old man with CHC. After routine treatment, local hyperplastic lesions remained. Photodynamic therapy with ALA was applied to the hyperplastic lesions and yielded satisfactory results, with no recurrence at 1 year. This case report describes a promising, effective method for the treatment of CHC.
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- 2022
43. Innocent until proven guilty: mechanisms and roles of Streptococcus- Candida interactions in oral health and disease.
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Xu, H., Jenkinson, H.F., and Dongari‐Bagtzoglou, A.
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ORAL hygiene , *STREPTOCOCCUS , *ORAL microbiology , *ORAL disease diagnosis , *MUCOUS membrane diseases - Abstract
Candida albicans and streptococci of the mitis group colonize the oral cavities of the majority of healthy humans. While C. albicans is considered an opportunistic pathogen, streptococci of this group are broadly considered avirulent or even beneficial organisms. However, recent evidence suggests that multi-species biofilms with these organisms may play detrimental roles in host homeostasis and may promote infection. In this review we summarize the literature on molecular interactions between members of this streptococcal group and C. albicans, with emphasis on their potential role in the pathogenesis of opportunistic oral mucosal infections. [ABSTRACT FROM AUTHOR]
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- 2014
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44. Advances in Humanized Mouse Models to Improve Understanding of HIV-1 Pathogenesis and Immune Responses
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Amy Gillgrass, Jocelyn M. Wessels, Jack X. Yang, and Charu Kaushic
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Mini Review ,Immunology ,Human immunodeficiency virus (HIV) ,Hiv management ,HIV Infections ,medicine.disease_cause ,mucosal infection ,immune response ,Pathogenesis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,co-infection ,medicine ,microbiota ,Immunology and Allergy ,Animals ,Humans ,business.industry ,pathogenesis ,Disease progression ,vaccines ,Additional research ,3. Good health ,Mucosal Infection ,Disease Models, Animal ,030104 developmental biology ,Humanized mouse ,HIV-1 ,humanized mouse ,lcsh:RC581-607 ,business ,030215 immunology - Abstract
Although antiretroviral therapy has transformed human immunodeficiency virus-type 1 (HIV-1) from a deadly infection into a chronic disease, it does not clear the viral reservoir, leaving HIV-1 as an uncurable infection. Currently, 1.2 million new HIV-1 infections occur globally each year, with little decrease over many years. Therefore, additional research is required to advance the current state of HIV management, find potential therapeutic strategies, and further understand the mechanisms of HIV pathogenesis and prevention strategies. Non-human primates (NHP) have been used extensively in HIV research and have provided critical advances within the field, but there are several issues that limit their use. Humanized mouse (Hu-mouse) models, or immunodeficient mice engrafted with human immune cells and/or tissues, provide a cost-effective and practical approach to create models for HIV research. Hu-mice closely parallel multiple aspects of human HIV infection and disease progression. Here, we highlight how innovations in Hu-mouse models have advanced HIV-1 research in the past decade. We discuss the effect of different background strains of mice, of modifications on the reconstitution of the immune cells, and the pros and cons of different human cells and/or tissue engraftment methods, on the ability to examine HIV-1 infection and immune response. Finally, we consider the newest advances in the Hu-mouse models and their potential to advance research in emerging areas of mucosal infections, understand the role of microbiota and the complex issues in HIV-TB co-infection. These innovations in Hu-mouse models hold the potential to significantly enhance mechanistic research to develop novel strategies for HIV prevention and therapeutics.
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- 2020
45. Verrucous carcinoma of the esophagus - a case report and literature review
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Thomas Frieling, D Müller, Ilka Melchior, Christoph Wullstein, Bernhard Hemmerlein, C. Kreysel, M. Blank, and Philipp Euler
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Male ,Pathology ,medicine.medical_specialty ,Endoscopic Mucosal Resection ,Esophageal Neoplasms ,Biopsy ,Endoscopic mucosal resection ,otorhinolaryngologic diseases ,medicine ,Carcinoma ,Humans ,Carcinoma, Verrucous ,Endoscopy, Digestive System ,Esophagus ,Eosinophilic esophagitis ,medicine.diagnostic_test ,Verrucous carcinoma ,business.industry ,Esophagogastroduodenoscopy ,Gastroenterology ,Pharyngitis ,Middle Aged ,medicine.disease ,Dysphagia ,Mucosal Infection ,medicine.anatomical_structure ,Treatment Outcome ,medicine.symptom ,business ,Deglutition Disorders - Abstract
Verrucous carcinoma of the esophagus is a rare disease leading to dysphagia, chest pain, and weight loss. The diagnosis is difficult because even repeated biopsies are often without tumor evidence. We present a patient with verrucous carcinoma of the esophagus and a literature review. A 64-year-old patient with dysphagia and sore throat received esophagogastroduodenoscopy illustrating segmental circumferential verrucous inflammation and Candida esophagitis in the middle part of the esophagus. Repeated mucosal biopsies revealed reactive hyperkeratosis of the squamous epithelium with minimal atypia but without ulcera, eosinophilic esophagitis, or suspicion of cancer. Mucosal infection with adenovirus, herpes simplex virus 1, human papilloma virus types, and cytomegaly virus was ruled out. Veruccous carcinoma was detected finally by endoscopic mucosal resection. The patient was successfully treated by esophageal resection. Tumor stage was G1, pT1b, pN0, L0, V0, Pn0, R0. The results suggest that macroscopic suspicion of verrucous esophageal carcinoma should lead to resections of larger tissue specimens by EMR to confirm the diagnosis. Das verruköse Ösophaguskarzinom ist eine seltene Erkrankung, die zu Dysphagie, Brustschmerzen und Gewichtsverlust führen kann. Die Diagnose ist schwierig, da selbst wiederholte Biopsien negativ sein können. Wir stellen einen Patienten mit verrukösem Ösophaguskarzinom und eine Literaturübersicht vor. Ein 64-jähriger Mann erhielt wegen Dysphagie und Sodbrennen eine Ösophagogastroduodenoskopie, die eine segmentale verruköse Entzündung und Soorinfektion im mittleren Ösophagus zeigte. Mehrmalige Biopsien ergaben eine reaktive Hyperkeratose des Plattenepithels mit minimalen Epithelatypien ohne Hinweise auf Ulzera, eosinophile Ösophagitis oder Karzinom. Mukosainfektionen mit Adenoviren, Herpes simplex Viren, Humanem Papilloma Virus und Cytomegalie Viren wurden ausgeschlossen. Das verruköse Karzinom wurde schließlich durch eine endoskopische Mukosaresektion (EMR) festgestellt. Der Patient wurde erfolgreich ösophagektomiert. Das Tumorstadium war G1, pT1b, pN0, L0, V0, Pn0, R0. Die Ergebnisse zeigen, dass bei endoskopischem V. a. ein verruköses Ösophaguskarzinom größere Gewebeentnahmen zur Sicherung der Diagnose erforderlich sind.
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- 2020
46. Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4
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Wen Shi Lee, Samantha L. Grimley, Mayank Khanna, Christopher A Gonelli, Charani Ranasinghe, Paula Clarisa Ellenberg, Stephen J. Kent, Thakshila Amarasena, Anthony D. Kelleher, Zhuofeng Li, and Damian F. J. Purcell
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0301 basic medicine ,CD4-Positive T-Lymphocytes ,Modified vaccinia Ankara ,Science ,viruses ,Immunology ,Immunization, Secondary ,CD8-Positive T-Lymphocytes ,Article ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Cytotoxic T cell ,Animals ,Adjuvants ,030212 general & internal medicine ,Antibody-dependent cell-mediated cytotoxicity ,AIDS Vaccines ,Vaccines ,Immunity, Cellular ,Multidisciplinary ,biology ,business.industry ,env Gene Products, Human Immunodeficiency Virus ,Interleukin-4 Receptor alpha Subunit ,Pigtail macaque ,biology.organism_classification ,Mucosal Infection ,Immunity, Humoral ,Granzyme B ,030104 developmental biology ,Preclinical research ,Granzyme K ,Macaca nemestrina ,business ,CD8 - Abstract
Inducing humoral, cellular and mucosal immunity is likely to improve the effectiveness of HIV-1 vaccine strategies. Here, we tested a vaccine regimen in pigtail macaques using an intranasal (i.n.) recombinant Fowl Pox Virus (FPV)-gag pol env-IL-4R antagonist prime, intramuscular (i.m.) recombinant Modified Vaccinia Ankara Virus (MVA)-gag pol-IL-4R antagonist boost followed by an i.m SOSIP-gp140 boost. The viral vector—expressed IL-4R antagonist transiently inhibited IL-4/IL-13 signalling at the vaccination site. The SOSIP booster not only induced gp140-specific IgG, ADCC (antibody-dependent cellular cytotoxicity) and some neutralisation activity, but also bolstered the HIV-specific cellular and humoral responses. Specifically, superior sustained systemic and mucosal HIV Gag-specific poly-functional/cytotoxic CD4+ and CD8+ T cells were detected with the IL-4R antagonist adjuvanted strategy compared to the unadjuvanted control. In the systemic compartment elevated Granzyme K expression was linked to CD4+ T cells, whilst Granzyme B/TIA-1 to CD8+ T cells. In contrast, the cytotoxic marker expression by mucosal CD4+ and CD8+ T cells differed according to the mucosal compartment. This vector-based mucosal IL-4R antagonist/SOSIP booster strategy, which promotes cytotoxic mucosal CD4+ T cells at the first line of defence, and cytotoxic CD4+ and CD8+ T cells plus functional antibodies in the blood, may prove valuable in combating mucosal infection with HIV-1 and warrants further investigation.
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- 2020
47. The Coronavirus PEDV Evades Type III Interferon Response Through the miR-30c-5p/SOCS1 Axis
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Fang Fu, Shuxin Qu, Lingling Shan, Keliang Wang, Pinghuang Liu, Ziqi Wang, Lu Wang, Mei Xue, Li Feng, Changlin Wang, and Wanhai Xu
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Microbiology (medical) ,IFN-λ ,medicine.medical_treatment ,coronavirus ,lcsh:QR1-502 ,medicine.disease_cause ,Microbiology ,lcsh:Microbiology ,03 medical and health sciences ,Immune system ,Interferon ,medicine ,SOCS1 ,Original Research ,030304 developmental biology ,Coronavirus ,0303 health sciences ,microRNA ,biology ,030306 microbiology ,Suppressor of cytokine signaling 1 ,miR-30c-5p ,PEDV ,biology.organism_classification ,Virology ,Mucosal Infection ,Cytokine ,Vero cell ,Porcine epidemic diarrhea virus ,medicine.drug - Abstract
Porcine epidemic diarrhea virus (PEDV) is an economically important pathogen that has evolved several mechanisms to evade type I IFN responses. Type III interferon (IFN-λ), an innate cytokine that primarily targets the mucosal epithelia, is critical in fighting mucosal infection in the host and has been reported to potently inhibit PEDV infection in vitro. However, how PEDV escapes IFN-λ antiviral response remains unclear. In this study, we found that PEDV infection induced significant IFN-λ expression in type I IFN-defective Vero E6 cells, but virus-induced endogenous IFN-λ did not reduce PEDV titers. Moreover, we demonstrated that PEDV escaped IFN-λ responses by substantially upregulating the suppressor of cytokine signaling protein 1 (SOCS1) expression, which impaired the induction of IFN-stimulated genes (ISGs) and dampened the IFN-λ antiviral response and facilitated PEDV replication in Vero E6 cells. We further showed that PEDV infection increased SOCS1 expression by decreasing host miR-30c-5p expression. MiR-30c-5p suppressed SOCS1 expression through targeting the 3′ untranslated region (UTR) of SOCS1. The inhibition of IFN-λ elicited ISGs expression by SOCS1 was specifically rescued by overexpression of miR-30c-5p. Collectively, our findings identify a new strategy by PEDV to escape IFN-λ-mediated antiviral immune responses by engaging the SOCS1/miR-30c axis, thus improving our understanding of its pathogenesis.
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- 2020
48. HLA-DRB1 alleles as predisposing and resisting factor in women suffering from vulvovaginal candidiasis
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Mehraban Falahati, Shirin Farahyar, Vahid Babaei, Niloufar Majdabadi, Tandis Razavi, and Shahram Teimourian
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Adult ,medicine.medical_specialty ,Disease ,Iran ,Polymerase Chain Reaction ,Immunity ,Recurrence ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Typing ,Allele ,Candida albicans ,HLA-DRB1 ,Alleles ,Candidiasis, Vulvovaginal ,DNA Primers ,biology ,business.industry ,Middle Aged ,biology.organism_classification ,Mucosal Infection ,Infectious Diseases ,Vagina ,Recurrent vulvovaginal candidiasis ,Female ,business ,HLA-DRB1 Chains - Abstract
Background Vulvovaginal candidiasis (VVC) is a vaginal mucosal infection that usually affects women in their reproductive age. When the signs of VVC persist on a daily basis or last for a long time and repeat at least three times per year, the disease is considered chronic and recurrent. Objective The purpose of this study was to evaluate the frequency of HLA-DRB1 alleles in patients with recurrent vulvovaginal candidiasis (RVVC). Study design 120 patients with RVVC and 136 age-matched healthy controls underwent low-resolution HLA-DRB typing performed using the polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. Results In the present work, we studied different genes that encode HLA-DRB (HLA-DRB1 / HLA-DRB3 / HLA-DRB4 / HLA-DRB5) and showed that HLA-DRB1×14, found in 25% of the patients. In the present study, the significant frequency of HLA-DRB1×10 in the control group suggests a resistant role of this allele to RVVC infections Conclusions In the HLA-DRB region, the DRB1×14 allele showed a higher frequency in the patients with RVVC than in the controls. Moreover, the higher frequency of DRB1×10 observed in the controls than in the patients with RVVC. These results demonstrate the HLA-DRB1 alleles are in relation with both susceptibility and immunity factors in RVVC infection and possible susceptible role of HLA-DRB1×14
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- 2020
49. Zika Virus Mucosal Infection Provides Protective Immunity
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Danyang Gong, Laura E. Martínez, Deisy Contreras, Gustavo Garcia, Vaithilingaraja Arumugaswami, and Ren Sun
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Male ,Sexual transmission ,T-Lymphocytes ,Immunology ,Viremia ,Antibodies, Viral ,Microbiology ,Epithelium ,Cell Line ,Zika virus ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Aedes ,Semen ,Virology ,Chlorocebus aethiops ,medicine ,Animals ,030212 general & internal medicine ,Viral shedding ,Vero Cells ,030304 developmental biology ,Subclinical infection ,0303 health sciences ,Mucous Membrane ,biology ,Zika Virus Infection ,Vaccination ,Immunity ,Rectum ,Epithelial Cells ,Zika Virus ,biology.organism_classification ,medicine.disease ,Antibodies, Neutralizing ,Mucosal Infection ,Mice, Inbred C57BL ,Disease Models, Animal ,Insect Science ,Pathogenesis and Immunity ,Female ,Immunization ,CD8 - Abstract
Zika virus (ZIKV) is a major human pathogen. ZIKV can replicate in female and male reproductive organs, thus facilitating the human-human transmission cycle. Viral shedding in the semen can increase the risk of ZIKV transmission through sexual mode. Therefore, the vaginal and anorectal mucosa are relevant sites for ZIKV infection. However, the pathobiology of ZIKV transmission through the rectal route is not well understood. Here, we utilize a mouse model system to investigate the immunopathological consequences following ZIKV infection of the rectal mucosa compared to a subcutaneous route of infection. We show that ZIKV-rectal inoculation results in viremia with subclinical infection. ZIKV infects the mucosal epithelium and submucosal dendritic cells, inducing immune and inflammatory cell infiltration. Rectal transmission of ZIKV resulted in the generation of serum-neutralizing antibody responses. Mass cytometry analyses of splenocytes showed a significantly reduced level of inflammatory monocyte and neutrophil cellular responses in the rectal route group. Furthermore, immunological priming through the rectal mucosa with an attenuated ZIKV strain resulted in significant protection from lethal subcutaneous ZIKV challenge, further eliciting robust memory CD4-positive (CD4(+)) and CD8(+) T-cell and ZIKV-specific serum-neutralizing antibody responses. Thus, our study provides deeper immunopathobiological insights on rectal transmission and highlights a rational strategy for mucosal immunization. This model system recapitulates clinical aspects of human ZIKV disease outcome, where most infections are well controlled and result in subclinical and asymptomatic outcomes. IMPORTANCE Zika virus is a clinically significant human pathogen that is primarily transmitted and spread by Aedes species mosquitoes but is also sexually transmissible. The recent pandemic in the Americas led to an unprecedented increase of newborn babies with developmental brain and eye abnormalities. To date, there is no licensed vaccine or therapeutic intervention available for the fight against ZIKV. Understanding the sexual transmission of ZIKV through vaginal and rectal routes is necessary to restrict virus transmission and spread. This study examines the early immunological and pathological consequences of rectal and subcutaneous routes of ZIKV infection using a mouse model. We characterized the primary target cells of ZIKV infection and the subsequent mucosal immune responses to infection, and we demonstrate the protective effect of mucosal rectal immunization using an attenuated ZIKV strain. This mucosal vaccination approach can be further developed to prevent future ZIKV outbreaks.
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- 2020
50. [Phages and vaccination: towards new opportunities?]
- Author
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Sylvie Margot, Aure Saulnier, and Veronique Barban
- Subjects
Vaccine research ,Phage display ,medicine.drug_class ,viruses ,medicine.medical_treatment ,Antibiotics ,Biology ,Virology ,Virus ,Mucosal Infection ,Vaccination ,Infectious Diseases ,Antigen ,medicine ,Adjuvant - Abstract
Bacteriophages, or phages, are ubiquitous microorganisms that only infect bacteria. They were briefly used, mainly in the West, in the early 20th century to treat human bacterial infections, before being replaced by antibiotics in the 1940s. In the 1970s, the phage display technology, which consists of presenting multiple copies of small polypeptides at the surface of the phage, led to consider phages as vaccine antigen producers. However, the technology potential for this use remains limited to small or truncated antigens that required the use of an adjuvant. Nowadays, phages are gaining a growing interest as vaccine antigen delivery vehicles. Evidence of the phage intrinsic adjuvant properties, which can be enhanced by targeting the particles to various eucaryotic cells, combined with a demonstrated inocuity in human and at low production cost make it possible to envisage in a near future the use of virus-based vaccines-like phagic particles (i.e. virus-like particles). This review describes, in a non-exhaustive way, some of the most promising technological approaches. In addition, there is a growing body of evidence from the literature showing that phages play a major role in the equilibrium of the human intestinal microbiota and protection against mucosal infection, opening new opportunities for vaccine research, targeting pathogens at the first natural host barrier protection.
- Published
- 2020
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