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Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. The immune response elicited by neurotropic viruses in the CNS is commanded mainly by microglia, which, together with other local cells, can secrete inflammatory cytokines to fight the infection. The most relevant neurotropic viruses are adenovirus (AdV), cytomegalovirus (CMV), enterovirus (EV), Epstein–Barr Virus (EBV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2), lymphocytic choriomeningitis virus (LCMV), and the newly discovered SARS-CoV-2. Several studies have associated a viral infection with systemic lupus erythematosus (SLE) and neuropsychiatric lupus (NPSLE) manifestations. This article will review the knowledge about viral infections, CNS pathologies, and the immune response against them. Also, it allows us to understand the relevance of the different viral proteins in developing neuronal pathologies, SLE and NPSLE. [ABSTRACT FROM AUTHOR]

The human respiratory syncytial virus (hRSV) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th)-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus. [ABSTRACT FROM AUTHOR]

Advances in understanding the mechanisms of cancer cells for evading the immune system surveillance, including how the immune system modulates the phenotype of tumours, have allowed the development of new therapies that benefit from this complex cellular network to specifically target and destroy cancer cells. Immunotherapy researchers have mainly focused on the discovery of tumour antigens that could confer specificity to immune cells to detect and destroy cancer cells, as well as on the mechanisms leading to an improved activation of effector immune cells. The Food and Drug Administration approval in 2010 of ipilumumab for melanoma treatment and of pembrolizumab in 2014, monoclonal antibodies against T-lymphocyte-associated antigen 4 and programmed cell death 1, respectively, are encouraging examples of how research in this area can successfully translate into clinical use with promising results. Currently, several ongoing clinical trials are in progress testing new anti-cancer therapies based on the enhancement of immune cell activity against tumour antigens. Here we discuss the general concepts related to immunotherapy and the recent application to the treatment of cancer with positive results that support their consideration of clinical application to patients. [ABSTRACT FROM AUTHOR]

Abstract Lipids play essential roles in the cell as components of cellular membranes, signaling molecules, and energy storage sources. Lipid droplets are cellular organelles composed of neutral lipids, such as triglycerides and cholesterol esters, and are also considered as cellular energy reserves, yet new functions have been recently associated with these structures, such as regulators of oxidative stress and cellular lipotoxicity, as well as modulators of pathogen infection through immune regulation. Lipid metabolism and lipid droplets participate in the infection process of many RNA viruses and control their replication and assembly, among others. Here, we review and discuss the contribution of lipid metabolism and lipid droplets over the replication cycle of RNA viruses, altogether pointing out potentially new pharmacological antiviral targets associated with lipid metabolism. [ABSTRACT FROM AUTHOR]

Despite political turmoil and economical crisis, research in Latin America has considerably advanced over recent decades. The present ‘Point of View’ outlines our perspectives on the working conditions, successes, difficulties, limitations, and challenges of biomedical scientific communities in four Latin American countries: Argentina (G.A.R.), Brazil (M.L.), Chile (A.K.), and Mexico (Y.R.). [ABSTRACT FROM AUTHOR]

Despite a troubled economic and political past, a tradition of fundamental research in immunology and infectious diseases has been fostered in Argentina, Brazil and Chile, as well as in other South American countries. [ABSTRACT FROM AUTHOR]

To assess the roles of serial engagement and kinetic proofreading in T cell receptor (TCR) internalization, we have developed a mathematical model of this process. Our determination of TCR down-regulation for an array of TCR mutants, interpreted in the context of the model, has provided new information about peptide-induced TCR internalization. The amount of TCR down-regulation increases to a maximum value and then declines as a function of the half-life of the bond between the TCR and peptide–major histocompatibility complex (pMHC). The model shows that this behavior, which reflects competition between serial engagement and kinetic proofreading, arises only if it is postulated that activated TCRs remain marked for internalization after dissociation from pMHC. The model also predicts that because of kinetic proofreading, the range of TCR-pMHC–binding half-lives required for T cell activation depends on the concentrations and localization of intracellular signaling molecules. We show here that kinetic proofreading provides an explanation for the different requirements for activation observed in naïve and memory T cells. [ABSTRACT FROM AUTHOR]

Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide?major histo-compatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding and dissociation from antigen. These parameters were also examined for variants derived from a Kd-restricted peptide that was recognized by a CTL clone. Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses. [ABSTRACT FROM AUTHOR]

Examines the importance of alpha beta T cells in the immune surveillance against infectious agents and endogenous malignant cell growth. Mechanism of antigen-specificity of the alpha beta T cell receptor; Activation of self-reactive T cells and development of autoimmunity; Components of the innate immune system.

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low‐grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)‐based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID‐19 pandemic, as these formulations helped to limit SARS‐CoV‐2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA‐based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses. [ABSTRACT FROM AUTHOR]

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.Identification of senescence-related markers in the brain and spinal cord of mice with asymptomatic HSV-1 brain infection and animals undergoing experimental autoimmune encephalomyelitis which parallels multiple sclerosis in humans. [ABSTRACT FROM AUTHOR]

Background: The exposure of human skin to leaves and branches of litre (Lithraea caustica), a Chilean endemic tree, induces a severe contact dermatitis characterized by swelling and pruritus in susceptible individuals. The allergenic priniciple of litre is 3–pentadecyl (10–enyl) catechol (litreol), which is structurally similar to the allergens isolated from poison oak and poison ivy. All of them belong to a family of compounds named urushiols. As a proelectrophilic allergen, litreol must be intracellularly activated before modifying proteins of individuals exposed to it. As a result, self–peptides derived from litreol–modified intracellular proteins would be presented in the context of class I MHC molecules. We hypothesized that CD8+ T lymphocytes would play a major role during the effector phase of the immune response induced by those modified peptides. In order to test this hypothesis, we investigated the cellular immune response to litreol in Balb/cJ mice. The role of the different lymphocyte subpopulations in this response was assessed by immunodepleting mice of CD4+ or CD8+ T lymphocytes using specific monoclonal antibodies (mAbs). We report the observation that the contact dermatitis induced by litreol has two components: a primary response which does not require TCRαβ+ T cells, and a secondary response mediated mainly by CD8+ T cells and regulated by CD4+ T cells. Our results show that CD8+ lymphocytes play a central role as effectors of the secondary response to litreol. Furthermore, our data suggest that two functionally different CD4+ T subpopulations serve as regulators of the CD8+ T cell function: a CD4+ T helper population sensitive to a low dose of the depleting mAb, and CD4+ T suppressor population which is eliminated only with a high dose of depleting mAb. [ABSTRACT FROM AUTHOR]

Lithraea caustica, or litre, a tree of the Anacardiaceae family that is endemic to the central region of Chile, induces a severe contact dermatitis in susceptible human beings. The allergen was previously isolated and characterized as a 3-(pentadecyl-10-enyl) catechol, a molecule belonging to the urushiol group of allergens isolated from poison ivy and poison oak plants. Because urushiols are pro-electrophilic haptens, it is believed that the reactive species are generated intracellularly by skin keratinocytes and Langerhans cells. The active species are presumed to modify self proteins which, after proteolytic processing, would generate immunogenic peptides carrying the hapten. The presence of a 15-carbon-length hydrophobic chain should impair antigen presentation of self-modified peptides by class I MHC molecules, either by steric hindrance or by limiting their sorting to the ER lumen. We have proposed that the shortening of the aliphatic chain by β-oxidation within peroxisomes and/or mitochondria should be a requirement for the antigen presentation process. To test this hypothesis we investigated the effect of drugs that modify the fatty acid metabolism on urushiol-induced contact dermatitis in mice. Clofibrate, a peroxisomal proliferator in mice, increased the immune response to the urushiols from litre by 50%. Conversely, tetradecyl glycidic acid, an inhibitor of the uptake of fatty acids by mitochondria, decreased the hypersensitivity to the hapten. An increase in the level in glutathione by treatment of the animals with 2-oxotiazolidin-4-carboxilic acid lowered the response. Those findings strongly support a role for the fatty acid oxidative metabolism in the processing and activation of urushiols in vivo. [ABSTRACT FROM AUTHOR]

The prevalence of food allergy has increased in recent years, especially among the pediatric population. Differences in the gut microbiota composition between children with FA and healthy children have brought this topic into the spotlight as a possible explanation for the increase in FA. The gut microbiota characteristics are acquired through environmental interactions starting early in life, such as type of delivery during birth and breastfeeding. The microbiota features may be shaped by a plethora of immunomodulatory mechanisms, including a predominant role of Tregs and the transcription factor FOXP3. Additionally, a pivotal role has been given to vitamin A and butyrate, the main anti-inflammatory metabolite. These observations have led to the study and development of therapies oriented to modifying the microbiota and metabolite profiles, such as the use of pre- and probiotics and the determination of their capacity to induce tolerance to allergens that are relevant to FA. To date, evidence supporting these approaches in humans is scarce and inconclusive. Larger cohorts and dose-titration studies are mandatory to evaluate whether the observed changes in gut microbiota composition reflect medical recovery and increased tolerance in pediatric patients with FA. In this article, we discuss the establishment of the microbiota, the immunological mechanisms that regulate the microbiota of children with food allergies, and the evidence in research focused on its regulation as a means to achieve tolerance to food allergens. [ABSTRACT FROM AUTHOR]

This review provides a comprehensive summary of evidence to explore the role and value of differential diagnosis in the management of Acute Respiratory Infections (ARIs) through point-of-care (POC) rapid testing in a post-pandemic scenario, paying particular attention to coronavirus disease 2019 (COVID-19), influenza, and respiratory syncytial virus (RSV). The document builds on a review of literature and policies and a process of validation and feedback by a group of seven experts from Latin America (LATAM). Evidence was collected to understand scientific and policy perspectives on the differential diagnosis of ARIs and POC rapid testing, with a focus on seven countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru. The evidence indicates that POC rapid testing can serve to improve ARI case management, epidemiological surveillance, research and innovation, and evidence-based decision-making. With multiple types of rapid tests available for POC, decisions regarding which tests to use require the consideration of the testing purpose, available resources, and test characteristics regarding accuracy, accessibility, affordability, and results turnaround time. Based on the understanding of the current situation, this document provides a set of recommendations for the implementation of POC rapid testing in LATAM, supporting decision-making and guiding efforts by a broad range of stakeholders. [ABSTRACT FROM AUTHOR]

Background We sought to identify potential antigens for discerning between humoral responses elicited after vaccination with CoronaVac (a severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] inactivated vaccine), natural infection, or breakthrough infection. Methods Serum samples obtained from volunteers immunized with CoronaVac (2 and 3 doses), breakthrough case patients, and from convalescent individuals were analyzed to determine the immunoglobulin (Ig) G responses against 3 structural and 8 nonstructural SARS-CoV-2 antigens. Results Immunization with CoronaVac induced higher levels of antibodies against the viral membrane (M) protein compared with convalescent subjects both after primary vaccination and after a booster dose. Individuals receiving a booster dose displayed equivalent levels of IgG antibodies against the nucleocapsid (N) protein, similar to convalescent subjects. Breakthrough case patients produced the highest antibody levels against the N and M proteins. Antibodies against nonstructural viral proteins were present in >50% of the convalescent subjects. Conclusions Vaccinated individuals elicited a different humoral response compared to convalescent subjects. The analysis of particular SARS-CoV-2 antigens could be used as biomarkers for determining infection in subjects previously vaccinated with CoronaVac. [ABSTRACT FROM AUTHOR]

During vertebrate development, the immune function is inefficient and is mainly controlled by innate defense. While there have been detailed studies of various aspects of innate immune function, the effects of this function in the growth of vertebrates is still not well known. Similarly, there is little information regarding how early endotoxin exposure would affect juvenile phenotypes, specifically in a non‐model mammal like a precocial rodent. We evaluated the response to an antigen and its cost in offspring of the rodent Octodon degus. We inoculated pups at 4 different ages (8, 15, 22 and 30 days after birth) with an antigen to determine the ontogeny and costs of the response to an endotoxin. We assessed changes in body mass, body temperature, sickness behavior and the levels of a key mediator of the inflammatory response, the cytokine interleukin‐1β. We also determined the effects of early endotoxin exposure on the resting metabolic rate of juvenile animals (i.e. 90 days after birth). The cytokine levels, body mass and body temperature were unaffected by time of inoculation and treatment. However, pups subjected to inoculation at 22 days after birth with the antigen showed reduced locomotion. Juvenile resting metabolic rate was not affected by early endotoxin exposure. These results suggest that the magnitude of O. degus responses would not change with age. We discuss whether the lack of effect of the response on body mass or body condition is caused by environmental variables or by the precocial characteristics of O. degus. [ABSTRACT FROM AUTHOR]

Objectives: Cell-based therapies involve the need to expand cell cultures ex vivo for their subsequent implantation in an autologous manner. An important limitation regarding this technology is the use of fetal bovine serum (FBS) that has critical safety limitations. Platelet-derived fractions represent an autologous source of growth factors that may be used for the expansion of these cell cultures. Periodontal ligament (PDL) cells comprise a heterogeneous cell population that may not necessarily respond in a uniform manner to proliferative stimuli. The aim of this study was to evaluate the ability of two platelet-derived fractions, platelet-rich plasma (PRP) and platelet-poor plasma (PPP) and FBS on the proliferative response of different subpopulations of PDL cell cultures. Materials and methods: PDL cells were characterized and then exposed to PRP, PPP, or FBS during 2, 5, or 14 days to analyze cell proliferation and clonogenic capability. Cell proliferation was evaluated through immunofluorescence for Ki67 and by tracing carboxyfluorescein diacetate succinimidyl ester (CFSE) dye in combination with mesenchymal stem cell markers using flow cytometry. Results: Both PRP and PPP stimulated PDL cell proliferation and their clonogenic ability. We found a significant increase of CD73- and CD90-positive cells after PRP or PPP treatment, compared to FBS. Otherwise, no differences were found regarding the response of CD146-or CD105-positive cells when stimulated with PRP, PPP, or FBS. Conclusion: PRP and PPP can stimulate the proliferation and clonogenicity of PDL cell populations including cells positive for CD90 and CD73 markers. Clinical relevance: These findings may have implications for future therapies aiming to stimulate periodontal regeneration using autologous growth factors. [ABSTRACT FROM AUTHOR]

Environmental temperature is a variable that influences all aspects of organisms, from physiological, e.g. immune function, and morphological traits to behavior. Recent studies have reported that environmental temperature modulates organisms’ thermoregulatory capacity and immune response, suggesting that trade-offs must be made between thermoregulation and immune function. Despite this, studies that evaluate this trade-off in developing endotherms are scarce. The aim of this study was to evaluate the effects of environmental temperature experienced during development on the response to an antigen and its energetic costs in the precocial rodent Octodon degus . To accomplish this, we acclimated pups from birth to weaning at temperatures of 15 °C and 30 °C. At weaning, animals were inoculated with lipopolysaccharide (LPS) and cytokine interleukin-1β levels, sickness behavior, changes in body temperature and basal metabolic rate, and body mass were measured. Our results showed that environmental temperature influences cytokine levels, body temperature, and some aspects of sickness behavior. Specifically, acclimatization at 30 °C has a suppressive effect on the response to LPS, possibly due to a control to avoid overproduction of interleukin-1β. Body mass and basal metabolic rate were not affected by environmental temperature experienced during development, but inoculation with LPS affected both variables. Our results suggest that ambient temperature may be a key factor that affects the response to an antigen in pups of O. degus; however, no evidence of a trade-off between thermoregulation and immune function was found here. [ABSTRACT FROM AUTHOR]

Human Respiratory Syncytial Virus (hRSV) is one of the major causes of acute lower respiratory tract infections (ALRTI) worldwide, leading to significant levels of immunocompromisation as well as morbidity and mortality in infants. Its main target of infection is the ciliated epithelium of the lungs and the host immune responses elicited is ineffective at achieving viral clearance. It is thought that the lack of effective immunity against hRSV is due in part to the activity of several viral proteins that modulate the host immune response, enhancing a Th2-like pro-inflammatory state, with the secretion of cytokines that promote the infiltration of immune cells to the lungs, with consequent damage. Furthermore, the adaptive immunity triggered by hRSV infection is characterized by weak cytotoxic T cell responses and secretion of low affinity antibodies by B cells. These features of hRSV infection have meant that, to date, no effective and safe vaccines have been licensed. In this article, we will review in detail the information regarding hRSV characteristics, pathology, and host immune response, along with several prophylactic treatments and vaccine prototypes. We will also expose significant data regarding the newly developed BCG-based vaccine that promotes protective cellular and humoral response against hRSV infection, which is currently undergoing clinical evaluation. [ABSTRACT FROM AUTHOR]

Oxidative stress derived from severe systemic inflammation promotes conversion from high-density lipoprotein HDL to oxidized HDL (oxHDL), which interacts with vascular endothelial cells (ECs). OxHDL acquires procoagulant features playing a role in modulating coagulation, which has been linked with organ failure in ICU patients. However, whether oxHDL elicits a ECs-mediated procoagulant phenotype generating organ failure and death, and the underlying molecular mechanism is not known. Therefore, we studied whether oxHDL-treated rats and high-oxHDL ICU patients exhibit a procoagulant phenotype and its association with kidney injury and mortality and the endothelial underlying molecular mechanism. Human ECs, oxHDL-treated rats and ICU patients were subjected to several cellular and molecular studies, coagulation analyses, kidney injury assessment and mortality determination. OxHDL-treated ECs showed a procoagulant protein expression reprograming characterized by increased E-/P-selectin and vWF mRNA expression through specific signaling pathways. OxHDL-treated rats exhibited a procoagulant phenotype and modified E-/P-selectin, vWF, TF and t-PA mRNA expression correlating with plasma TF, t-PA and D-dimer. Also, showed increased death events and the relative risk of death, and increased creatinine, urea, BUN/creatinine ratio, KIM-1, NGAL, β2M, and decreased eGFR, all concordant with kidney injury, correlated with plasma TF, t-PA and D-dimer. ICU patients showed correlation between plasma oxHDL and increased creatinine, cystatin, BUN, BUN/creatinine ratio, KIM-1, NGAL, β2M, and decreased GFR. Notably, ICU high-oxHDL patients showed decreased survival. Interestingly, altered coagulation factors TF, t-PA and D-dimer correlated with both increased oxHDL levels and kidney injury markers, indicating a connection between these factors. Increased circulating oxHDL generates an endothelial-dependent procoagulant phenotype that associates with acute kidney injury and increased risk of death. [ABSTRACT FROM AUTHOR]

LAG-3 is a type I transmembrane protein expressed on immune cells, such as activated T cells, and binds to MHC class II with high affinity. LAG-3 is an inhibitory receptor, and its multiple biological activities on T cell activation and effector functions play a regulatory role in the immune response. Immunotherapies directed at immune checkpoints, including LAG-3, have become a promising strategy for controlling malignant tumors and chronic viral diseases. Several studies have suggested an association between the expression of LAG-3 with an inadequate immune response during respiratory viral infections and the susceptibility to reinfections, which might be a consequence of the inhibition of T cell effector functions. However, important information relative to therapeutic potential during acute viral lower respiratory tract infections and the mechanism of action of the LAG-3 checkpoint remains to be characterized. In this article, we discuss the contribution of LAG-3 to the impairment of T cells during viral respiratory infections. Understanding the host immune response to respiratory infections is crucial for developing effective vaccines and therapies. [ABSTRACT FROM AUTHOR]

Autoimmune diseases, such as systemic lupus erythematosus (SLE), result from deficiencies in self-antigen tolerance processes, which require regulated dendritic cell (DC) function. In this study we evaluated the phenotype of DCs during the onset of SLE in a mouse model, in which deletion of the inhibitory receptor FcγRIIb leads to the production of anti-nuclear antibodies and glomerulonephritis. Splenic DCs from FcγRIIb-deficient mice suffering from SLE showed increased expression of co-stimulatory molecules. Furthermore, diseased mice showed an altered function of the nuclear factor-κB (NF-κB) transcription factor, which is involved in DC maturation. Compared with healthy animals, expression of the inhibitory molecule IκB-α was significantly decreased in mice suffering from SLE. Consistently, pharmacological inhibition of NF-κB activity in FcγRIIb-deficient mice led to reduced susceptibility to SLE and prevented symptoms, such as anti-nuclear antibodies and kidney damage. Our data suggest that the occurrence of SLE is significantly influenced by alterations of NF-κB function, which can be considered as a new therapeutic target for this disease. [ABSTRACT FROM AUTHOR]

Presents a corrigendum in the article 'Activated TCRs remain marked for internalization after dissociation from pMHC,' by Daniel Coombs, Alexis M. Kalergis, Stanley G. Nathenson, Carla Wofsy and Byron Goldstein, published in third issue of 'Nature Immunology' for 2002.

We analyze 6 months of Twitter conversations related to the Chilean Covid-19 vaccination process, in order to understand the online forces that argue for or against it and suggest effective digital communication strategies. Using AI, we classify accounts into four categories that emerge from the data as a result of the type of language used. This classification naturally distinguishes pro- and anti-vaccine activists from moderates that promote or inhibit vaccination in discussions, which also play a key role that should be addressed by public policies. We find that all categories display relatively constant opinions, but that the number of tweeting accounts grows in each category during controversial periods. We also find that accounts disfavoring vaccination tend to appear in the periphery of the interaction network, which is consistent with Chile's high immunization levels. However, these are more active in addressing those favoring vaccination than vice-versa, revealing a potential communication problem even in a society where the antivaccine movement has no central role. Our results highlight the importance of social network analysis to understand public discussions and suggest online interventions that can help achieve successful immunization campaigns. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections (LRTIs) produced by viruses are the most frequent cause of morbidity and mortality in children younger than 5 years of age. The immune response triggered by viral infection can induce a strong inflammation in the airways and cytokines could be considered as biomarkers for disease severity as these molecules modulate the inflammatory response that defines the outcome of patients. Aiming to predict the severity of disease during respiratory tract infections, we conducted a 1-year follow-up observational study in infants who presented upper or lower respiratory tract infections caused by seasonal respiratory viruses. At the time of enrollment, nasopharyngeal swabs (NPS) were obtained from infants to measure mRNA expression and protein levels of IL-3, IL-8, IL-33, and thymic stromal lymphopoietin. While all cytokines significantly increased their protein levels in infants with upper and lower respiratory tract infections as compared to control infants, IL-33 and IL-8 showed a significant increase in respiratory syncytial virus (RSV)-infected patients with LRTI as compared to patients with upper respiratory tract infection. We also found higher viral loads of RSV-positive samples with a greater IL-8 response at the beginning of the symptoms. Data obtained in this study suggest that both IL-8 and IL-33 could be used as biomarkers for clinical severity for infants suffering from LRTIs caused by the RSV. IL-33 and IL-8 are significantly increased in patients infected with lower respiratory tract infection caused by the respiratory syncytial virus, as compared to patients with upper respiratory tract infection. These molecules are potential severity biomarkers. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) is an autoimmune disorder like systemic lupus erythematosus (SLE). Both SLE and CLE characterize autoantibody secretion and immune cell recruitment. In particular, CLE can be divided into three more frequent types, varying in the severity of the skin lesions they present. The role of type I IFN was shown to be one of the leading causes of the development of this pathology in the skin. Different treatments have been developed and tested against these different variants of CLE to decrease the increasing levels of CLE in humans. In this article, a literature revision discussing the similarities between SLE and CLE is carried out. In addition, new advances in understanding the development of CLE and the leading treatments being evaluated in animal models and clinical trials are reviewed. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are cellular organelles rich in neutral lipids such as triglycerides and cholesterol esters that are coated by a phospholipid monolayer and associated proteins. LDs are known to play important roles in the storage and availability of lipids in the cell and to serve as a source of energy reserve for the cell. However, these structures have also been related to oxidative stress, reticular stress responses, and reduced antigen presentation to T cells. Importantly, LDs are also known to modulate viral infection by participating in virus replication and assembly. Here, we review and discuss the interplay between neutral lipid metabolism and LDs in the replication cycle of different DNA viruses, identifying potentially new molecular targets for the treatment of viral infections. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease characterized by a robust inflammatory response against myelin sheath antigens, which causes astrocyte and microglial activation and demyelination of the central nervous system (CNS). Multiple genetic predispositions and environmental factors are known to influence the immune response in autoimmune diseases, such as MS, and in the experimental autoimmune encephalomyelitis (EAE) model. Although the predisposition to suffer from MS seems to be a multifactorial process, a highly sensitive period is pregnancy due to factors that alter the development and differentiation of the CNS and the immune system, which increases the offspring's susceptibility to develop MS. In this regard, there is evidence that thyroid hormone deficiency during gestation, such as hypothyroidism or hypothyroxinemia, may increase susceptibility to autoimmune diseases such as MS. In this review, we discuss the relevance of the gestational period for the development of MS in adulthood. [ABSTRACT FROM AUTHOR]

Carbon monoxide ( CO) has been recently reported as the main anti-inflammatory mediator of the haem-degrading enzyme haem-oxygenase 1 ( HO-1). It has been shown that either HO-1 induction or CO treatment reduces the ability of monocytes to respond to inflammatory stimuli, such as lipopolysaccharide ( LPS), due to an inhibition of the signalling pathways leading to nuclear factor- κB, mitogen-activated protein kinases and interferon regulatory factor 3 activation. Hence, it has been suggested that CO impairs the stimulation of the Toll-like receptor 4 ( TLR4)/myeloid differentiation factor-2 (MD2) complex located on the surface of immune cells. However, whether CO can negatively modulate the surface expression of the TLR4/ MD2 complex in immune cells remains unknown. Here we report that either HO-1 induction or treatment with CO decreases the surface expression of TLR4/ MD2 in dendritic cells ( DC) and neutrophils. In addition, in a septic shock model of mice intraperitoneally injected with lipopolysaccharide ( LPS), prophylactic treatment with CO protected animals from hypothermia, weight loss, mobility loss and death. Further, mice pre-treated with CO and challenged with LPS showed reduced recruitment of DC and neutrophils to peripheral blood, suggesting that this gas causes a systemic tolerance to endotoxin challenge. No differences in the amount of innate cells in lymphoid tissues were observed in CO-treated mice. Our results suggest that CO treatment reduces the expression of the TLR4/ MD2 complex on the surface of myeloid cells, which renders them resistant to LPS priming in vitro, as well as in vivo in a model of endotoxic shock. [ABSTRACT FROM AUTHOR]

Neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3), NT-4, and NT-5, are proteins involved in several important functions of the central nervous system. The activation of the signaling pathways of these neurotrophins, or even by their immature form, pro-neurotrophins, starts with their recognition by cellular receptors, such as tropomyosin receptor kinase (Trk) and 75 kD NT receptors (p75NTR). The Trk receptor is considered to have a high affinity for attachment to specific neurotrophins, while the p75NTR receptor has less affinity for attachment with neurotrophins. The correct functioning of these signaling pathways contributes to proper brain development, neuronal survival, and synaptic plasticity. Unbalanced levels of neurotrophins and pro-neurotrophins have been associated with neurological disorders, illustrating the importance of these molecules in the central nervous system. Furthermore, reports have indicated that viruses can alter the normal levels of neurotrophins by interfering with their signaling pathways. This work discusses the importance of neurotrophins in the central nervous system, their signaling pathways, and how viruses can affect them. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium bovis strain used as a vaccine to prevent Mycobacterium tuberculosis (M. tb) infection. Its ability to potentiate the immune response induced by other vaccines and to promote nonspecific immunomodulatory effects has been described. These effects can be triggered by epigenetic reprogramming and metabolic shifts on innate immune cells, a phenomenon known as trained immunity. The induction of trained immunity may contribute to explain why BCG vaccination effectively decreases disease symptoms caused by pathogens different from M. tb. This article explains the importance of BCG immunization and the possible mechanisms associated with the induction of trained immunity, which might be used as a strategy for rapid activation of the immune system against unrelated pathogens. Bacillus Calmette-Guérin (BCG) has been the most widely used vaccine globally to induce immunity against Mycobacterium tuberculosis (M. tb). This vaccine is an important prophylactic measure to reduce the progression of tuberculous pulmonary disease. BCG is administered, in most cases, during the first days of life and has led to a decrease in neonatal tuberculosis deaths. BCG can promote immunity against other non-tuberculosis mycobacteria, such as Mycobacterium leprae , Mycobacterium ulcerans , Mycobacterium avium , Mycobacterium intracellulare , and Mycobacterium abscessus. BCG can also contribute to the control of opportunistic pathogens. BCG can induce the expansion of T cells that recognize epitopes against other bacteria (different than M. tb) and viruses [e.g., severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)]. Although the underlying mechanism for cross-protection is not yet fully understood, it is thought to rely on epigenetic changes and metabolic modifications on immune cells. New data have suggested an association between decreased mortality rates due to SARS-CoV-2 infection with a high rate of BCG vaccination, suggesting that this vaccine might potentially generate cross-protective immunity against this virus, which remains to be robustly tested. [ABSTRACT FROM AUTHOR]

Adequate iodine nutrition is crucial for all mammals by playing his starring role as a component of thyroid hormones, which are key regulators of cellular processes for life such as differentiation, growth, function, and metabolism. Deficiency or excess of iodine in the diet are worldwide highly frequent conditions that are responsible of health problems like hypothyroidism, hypothyroxinemia, goiter, thyroiditis, hyperthyroidism, and autoimmune thyroid diseases among others. The incorporation of iodine in salt or other nutrients resolved the consequences of severe iodine deficiency like goiter, cretinism. However, this strategy in several countries led to other ailments like Hashimoto autoimmune thyroiditis, hyperthyroidism, and hypothyroidism. The goal of this review is to analyze and discuss the different aspects of iodine nutrition for human health comprising its biological role through thyroid hormones, pathogen control, and the regulation of the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (h MPV) is the second most common cause of acute lower respiratory tract infections in children, causing a significant public health burden worldwide. Given that h MPV can repeatedly infect the host without major antigenic changes, it has been suggested that h MPV may have evolved molecular mechanisms to impair host adaptive immunity and, more specifically, T-cell memory. Recent studies have shown that h MPV can interfere with superantigen-induced T-cell activation by infecting conventional dendritic cells ( DCs). Here, we show that h MPV infects mouse DCs in a restricted manner and induces moderate maturation. Nonetheless, h MPV-infected DCs are rendered inefficient at activating naive antigen-specific CD4+ T cells ( OT-II), which not only display reduced proliferation, but also show a marked reduction in surface activation markers and interleukin-2 secretion. Decreased T-cell activation was not mediated by interference with DC-T-cell immunological synapse formation as recently described for the human respiratory syncytial virus (hRSV), but rather by soluble factors secreted by h MPV-infected DCs. These data suggest that although h MPV infection is restricted within DCs, it is sufficient to interfere with their capacity to activate naive T cells. Altogether, by interfering with DC function and productive priming of antigen-inexperienced T cells, h MPV could impair the generation of long-term immunity. [ABSTRACT FROM AUTHOR]

Abstract: Since the preferential body temperature should positively correlate with physiological performance, behavioural fever should enhance an organism’s immune response under an immune challenge. Here we have studied the preferential body temperature (T p) and its consequences on immune response performance after an immune challenge in larvae of Tenebrio molitor. We evaluated T p and immune responses of larvae following a challenge with various concentrations of lipopolysaccharide (LPS), and we studied the correlation between T p and two immune traits, namely antibacterial and phenoloxidase (PO) activities. Larvae that were immune challenged with higher LPS concentrations (C 50 and C 100) preferred in average, warmer temperatures than did larvae challenged with lower concentrations (C 0 and C 25). T p of C 25–C 100 (challenged)-mealworms was 2.3°C higher than of C 0 (control) larvae. At lower LPS concentration immune challenge (C 0 and C 25) antibacterial activity correlated positively with T p, but at C 50 and C 100 correlation was lose. PO activity was higher at higher LPS concentration, but its magnitude of response did not correlate with T p Our data suggest that behavioural fever may have a positive effect on host performance by enhancing antibacterial response under a low pathogen load situation. [Copyright &y& Elsevier]

Dendritic cells (DCs) are phagocytic professional antigen-presenting cells that can prime naive T cells and initiate anti-bacterial immunity. However, several pathogenic bacteria have developed virulence mechanisms to impair DC function. For instance, Salmonella enterica serovar Typhimurium can prevent DCs from activating antigen-specific T cells. In addition, it has been described that the Salmonella Pathogenicity Island 1 (SPI-1), which promotes phagocytosis of bacteria in non-phagocytic cells, can suppress this process in DCs in a phosphatidylinositol 3-kinase (PI3K) -dependent manner. Both mechanisms allow Salmonella to evade host adaptive immunity. Recent studies have shown that IgG-opsonization of Salmonella can restore the capacity of DCs to present antigenic peptide-MHC complexes and prime T cells. Interestingly, T-cell activation requires Fcγ receptor III (FcγRIII) expression over the DC surface, suggesting that this receptor could counteract both antigen presentation and phagocytosis evasion by bacteria. We show that, despite IgG-coated Salmonella retaining its capacity to secrete anti-capture proteins, DCs are efficiently capable of engulfing a large number of IgG-coated bacteria. These results suggest that DCs employ another mechanism to engulf IgG-coated Salmonella, different from that used for free bacteria. In this context, we noted that DCs do not employ PI3K, actin cytoskeleton or dynamin to capture IgG-coated bacteria. Likewise, we observed that the capture is an FcγR-independent mechanism. Interestingly, these internalized bacteria were rapidly targeted for degradation within lysosomal compartments. Hence, our results suggest a novel mechanism in DCs that does not employ PI3K/actin cytoskeleton/dynamin/FcγRs to engulf IgG-coated Salmonella, is not affected by anti-capture SPI-1-derived effectors and enhances DC immunogenicity, bacterial degradation and antigen presentation. [ABSTRACT FROM AUTHOR]

Abstract: The interaction between the T cell receptor (TCR) and the peptide-MHC complex (pMHC) at the interface between the T cell and the antigen presenting cell (APC) is the main event controlling the specificity of antigen recognition by T cells. It is thought that TCR/pMHC binding kinetics are critical for the selection of the T cell repertoire in the thymus, as well as the activation of mature T cells in the periphery. One of the binding parameters that conditions T cell activation by pMHC ligands is the half-life of the TCR/pMHC interaction. This kinetic parameter is highly significant for the regulation of T cell activation and therefore determines the capacity of T cells to respond against pathogen- and tumor-derived antigens, avoiding self-reactivity. Several studies support the notion that T cells are activated only by TCR/pMHC interactions that are above a threshold of half-life. pMHC complexes that bind TCRs with half-lives below that threshold behave as null or antagonistic ligands. However, since prolonged half-lives can also impair T cell activation, there seems to be a ceiling for the TCR/pMHC half life that leads to efficient activation of T cells. According to these observations, efficient T cell activation would require an optimal half-life of TCR/pMHC interaction. These kinetic restrictions for T cell activation are important to generate a protective adaptive immune response minimizing cross-reactivity against self-constituents. The nature of the TCR/pMHC interaction defines in the thymus whether a thymocyte develops into a mature T cell or is eliminated by apoptosis. In addition, the kinetics of TCR/pMHC binding can determine the type of response shown by mature T cells in the periphery. Although several studies have focused on the modulation of T cell function by the affinity of the TCR/pMHC interaction, the binding kinetics rules governing T cell activation remain poorly understood. Here we review recent data and propose a new model for the regulation of T cell function by TCR/pMHC binding kinetics. [Copyright &y& Elsevier]

Summary: Orthohantaviruses, previously named hantaviruses, cause two emerging zoonotic diseases: haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Overall, over 200 000 cases are registered every year worldwide, with a fatality rate ranging between 0·1% and 15% for HFRS and between 20% and 40% for HCPS. No specific treatment or vaccines have been approved by the U.S. Food and Drug Administration (FDA) to treat or prevent hantavirus‐caused syndromes. Currently, little is known about the mechanisms at the basis of hantavirus‐induced disease. However, it has been hypothesized that an excessive inflammatory response plays an essential role in the course of the disease. Furthermore, the contributions of the cellular immune response to either viral clearance or pathology have not been fully elucidated. This article discusses recent findings relative to the immune responses elicited to hantaviruses in subjects suffering HFRS or HCPS, highlighting the similarities and differences between these two clinical diseases. Also, we summarize the most recent data about the cellular immune response that could be important for designing new vaccines to prevent this global public health problem. [ABSTRACT FROM AUTHOR]

Neurobehavioral alterations and cognitive impairment are common phenomena that represent neuropsychiatric disorders and can be triggered by an exacerbated immune response against pathogens, brain injury, or autoimmune diseases. Pro-inflammatory molecules, such as cytokines and chemokines, are produced in the brain by resident cells, mainly by microglia and astrocytes. Brain infiltrating immune cells constitutes another source of these molecules, contributing to an impaired neurological synapse function, affecting typical neurobehavioral and cognitive performance. Currently, there is increasing evidence supporting the notion that behavioral alterations and cognitive impairment can be associated with respiratory viral infections, such as human respiratory syncytial virus, influenza, and SARS-COV-2, which are responsible for endemic, epidemic, or pandemic outbreak mainly in the winter season. This article will review the brain′s pro-inflammatory response due to infection by three highly contagious respiratory viruses that are the leading cause of acute respiratory illness, morbidity, and mobility in infants, immunocompromised and elderly population. How these respiratory viral pathogens induce increased secretion of pro-inflammatory molecules and their relationship with the alterations at a behavioral and cognitive level will be discussed. [ABSTRACT FROM AUTHOR]

The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates. [ABSTRACT FROM AUTHOR]

Provides information on a study generating T cell receptor (TCR) ... chain transgenic mice in a TCR ...-deficient background and using these mice to further analyze the interaction between the TCR ... chain and the vesicular stomatitis virus (VSV) peptide. Methodology and materials used to conduct the study; Results of the study.

The human respiratory syncytial virus (hRSV) is the most common infectious agent that affects children before two years of age. hRSV outbreaks cause a significant increase in hospitalizations during the winter season associated with bronchiolitis and pneumonia. Recently, neurologic alterations have been associated with hRSV infection in children, which include seizures, central apnea, and encephalopathy. Also, hRSV RNA has been detected in cerebrospinal fluids (CSF) from patients with neurological symptoms after hRSV infection. Additionally, previous studies have shown that hRSV can be detected in the lungs and brains of mice exposed to the virus, yet the potential effects of hRSV infection within the central nervous system (CNS) remain unknown. Here, using a murine model for hRSV infection, we show a significant behavior alteration in these animals, up to two months after the virus exposure, as shown in marble-burying tests. hRSV infection also produced the expression of cytokines within the brain, such as IL-4, IL-10, and CCL2. We found that hRSV infection alters the permeability of the blood–brain barrier (BBB) in mice, allowing the trespassing of macromolecules and leading to increased infiltration of immune cells into the CNS together with an increased expression of pro-inflammatory cytokines in the brain. Finally, we show that hRSV infects murine astrocytes both, in vitro and in vivo. We identified the presence of hRSV in the brain cortex where it colocalizes with vWF, MAP-2, Iba-1, and GFAP, which are considered markers for endothelial cells, neurons, microglia, and astrocyte, respectively. hRSV-infected murine astrocytes displayed increased production of nitric oxide (NO) and TNF-α. Our results suggest that hRSV infection alters the BBB permeability to macromolecules and immune cells and induces CNS inflammation, which can contribute to the behavioral alterations shown by infected mice. A better understanding of the neuropathy caused by hRSV could help to reduce the potential detrimental effects on the CNS in hRSV-infected patients. [ABSTRACT FROM AUTHOR]

Human respiratory syncytial virus infection is a leading cause of pediatric morbidity and mortality. A previous murine study showed that during severe acute respiratory infections the virus invades the central nervous system, and that infected animals evolve with long-lasting learning difficulties associated with long-term potentiation impairment in their hippocampus. We hypothesized here that human infants who presented a severe episode of respiratory syncytial virus infection before 6 months of age would develop long-term learning difficulties. We measured the acquisition of the native phoneme repertoire during the first year, a milestone in early human development, comprising a reduction in the sensitivity to the irrelevant nonnative phonetic information and an increase in the sensitivity to the information relevant for the native one. We found that infants with a history of severe respiratory infection by the human respiratory syncytial virus presented poor distinction of native and nonnative phonetic contrasts at 6 months of age, and remained atypically sensitive to nonnative contrasts at 12 months, which associated with weak communicative abilities. Our results uncover previously unknown long-term language learning difficulties associated with a single episode of severe respiratory infection by the human respiratory syncytial virus, which could relate to memory impairments. [ABSTRACT FROM AUTHOR]

Background: Group B Streptococcus (GBS) is the leading cause of invasive neonatal infection. In this study, we aimed to evaluate the analytical validation of qualitative real-time polymerase chain reaction (qPCR) as a means to detect GBS.Methods: Genomic DNA (gDNA) was purified from 12 ATCC bacterial strains, two belonging to GBS and the remainder acting as negative controls. Additionally, gDNA was isolated from 21 strains of GBS from various serotypes (Ia, Ib and II-VIII). All gDNA was used to evaluate the analytical validation of the qPCR method employing a specific Taqman probe. Inclusivity, exclusivity, anticipated reportable range, the limit of detection and robustness were evaluated. The methods used are described in international guidelines and other existing reports. The performance of this qPCR method for detecting GBS was compared to other microbiological methods used with vaginal-rectal samples from pregnant women.Results: Our qPCR method for detecting GBS was analytically validated. It has a limit of detection of 0.7 GE/μL and 100% analytical specificity. It detects all strains of GBS with the same level of performance as microbiological methods.Conclusion: Data suggest that this qPCR method performs adequately as a means to detect GBS in vaginal-rectal swabs from pregnant women. [ABSTRACT FROM AUTHOR]

Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS. [ABSTRACT FROM AUTHOR]

Pathogenicity island excision is a phenomenon that occurs in several Salmonella enterica serovars and other members of the family Enterobacteriaceae. ROD21 is an excisable pathogenicity island found in the chromosome of S. Enteritidis, S. Dublin and S. Typhi among others, which contain several genes encoding virulence-associated proteins. Excision of ROD21 may play a role in the ability of S. Enteritidis to cause a systemic infection in mice. Our previous studies have shown that Salmonella strains unable to excise ROD21 display a reduced ability to colonize the liver and spleen. In this work, we determined the kinetics of ROD21 excision in vivo in C57BL/6 mice and its effect on virulence. We quantified bacterial burden and excision frequency in different portions of the digestive tract and internal organs throughout the infection. We observed that the frequency of ROD21 excision was significantly increased in the bacterial population colonizing mesenteric lymph nodes at early stages of the infective cycle, before 48 hours post-infection. In contrast, excision frequency remained very low in the liver and spleen at these stages. Interestingly, excision increased drastically after 48 h post infection, when intestinal re-infection and mortality begun. Moreover, we observed that the inability to excise ROD21 had a negative effect on S. Enteritidis capacity to translocate from the intestine to deeper organs, which correlates with an abnormal transcription of invA in the S. Enteritidis strain unable to excise ROD21. These results suggest that excision of ROD21 is a genetic mechanism required by S. Enteritidis to produce a successful invasion of the intestinal epithelium, a step required to generate systemic infection in mice. Author summary: Salmonella is a bacterial genus that causes foodborne illnesses worldwide. The ability of Salmonella to cause disease is related to the presence of Pathogenicity Islands (PAIs), which are clusters of genes within the bacterial chromosome that are involved in virulence. Interestingly, some PAIs excise and re-integrate into the bacterial chromosome, which is a process probably involved in the capacity of Salmonella to cause infection in their hosts. Here we show that the excision of Region of Difference 21 (ROD21), one of the excisable PAIs within the genome of Salmonella enterica serovar Enteritidis, occurs with high frequency in the mesenteric lymph node at early stages of infection, suggesting that excision is required by S. Enteritidis to reach this organ from the intestinal tract. Accordingly, S. Enteritidis strains unable to excise ROD21 are unable to invade intestinal host cells, delaying the infective cycle and showing attenuated virulence. We propose that ROD21 excision in vivo is required by S. Enteritidis to cross the intestinal barrier, a fundamental step to further colonize deep organs, due to modulation of virulence genes transcription. Thus, ROD21 excision may play an important role in the capacity of the bacteria to cause a successful systemic infection in the mouse. Our data suggest that the excision of PAIs is a mechanism used by Salmonella and probably other Gram-negative enterobacteria to modulate the expression of virulence genes and may provide insights to design novel therapies to control the infection caused by these pathogens. [ABSTRACT FROM AUTHOR]

Summary: Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme‐oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL‐Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti‐nuclear antibody‐positive mice throughout 60–70 days, and the clinical score was evaluated. Long‐term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL‐Faslpr lupus‐prone mice. Additionally, decreased levels of anti‐nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone‐loaded tolDCs could improve only some SLE symptoms and reduced anti‐nuclear antibodies. This is the first study to evaluate antigen‐specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity. [ABSTRACT FROM AUTHOR]

• T-cells from mice immunized with rSIP/AbISCO-100 conferred protection against Group B streptococcus. • Opsonophagocytic serum from mice immunized with rSIP/AbISCO-100 conferred protection against Group B streptococcus. • Surface Immunogenic protein could be a potential vaccine candidate against Group B streptococcus. Group B Streptococcus (GBS) represents one of the most common causes of bacterial infection in neonates; it is also associated with premature childbirth and stillbirth. A vaccine against GBS is needed, but no approved vaccines are yet available. The Surface Immunogenic Protein (SIP) of GBS is conserved in all serotypes and had been reported to be a good vaccine prototype in a mouse model of GBS infection. Also, we have previously shown that both subcutaneous and oral immunization with rSIP can induce an efficient immune response that decreases GBS vaginal colonization in mice. In this study, we show that a vaccine based on a mixture of rSIP and AbISCO-100 adjuvant reduces GBS vaginal colonization in mice and induces antibodies with opsonophagocytic activities. Moreover, the passive transfer of sera and total T-cells from mice immunized with rSIP mixed with AbISCO-100 to unvaccinated mice decreases vaginal GBS colonization in an infected mouse. This is the first report of cellular immunity associated with rSIP-based vaccine testing in a mouse model of GBS infection. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether circulating endothelial cells from septic shock patients and from nonseptic shock patients are transformed in activated fibroblast by changing the expression level of endothelial and fibrotic proteins, whether the level of the protein expression change is associated with the amount of administered resuscitation fluid, and whether this circulating endothelial cell protein expression change is a biomarker to predict sepsis survival.Design: Prospective study.Setting: Medical-surgical ICUs in a tertiary care hospital.Patients: Forty-three patients admitted in ICU and 22 healthy volunteers.Interventions: None.Measurements and Main Results: Circulating mature endothelial cells and circulating endothelial progenitor cells from septic shock and nonseptic shock patients showed evidence of endothelial fibrosis by changing the endothelial protein expression pattern. The endothelial proteins were downregulated, whereas fibroblast-specific markers were increased. The magnitude of the expression change in endothelial and fibrotic proteins was higher in the septic shock nonsurvivors patients but not in nonseptic shock. Interestingly, the decrease in the endothelial protein expression was correlated with the administered resuscitation fluid better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in the septic shock nonsurvivors patients but not in nonseptic shock. Notably, the significant difference between endothelial and fibrotic protein expression indicated a nonsurvival outcome in septic shock but not in nonseptic shock patients. Remarkably, area under the receiver operating characteristic curve analysis showed that endothelial protein expression levels predicted the survival outcome better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in septic shock but not in nonseptic shock patients.Conclusions: Circulating endothelial cells from septic shock patients are acutely converted into fibroblasts. Endothelial and fibrotic protein expression level are associated with resuscitation fluid administration magnitude and can be used as biomarkers for an early survival diagnosis of sepsis. [ABSTRACT FROM AUTHOR]

The immune system is responsible for defending the host from a large variety of potential pathogens, while simultaneously avoiding immune reactivity towards self-components. Self-tolerance has to be tightly maintained throughout several central and peripheral processes; immune checkpoints are imperative for regulating the immunity/tolerance balance. Dendritic cells (DCs) are specialized cells that capture antigens, and either activate or inhibit antigen-specific T cells. Therefore, they play a key role at inducing and maintaining immune tolerance. DCs that suppress the immune response have been called tolerogenic dendritic cells (tolDCs). Given their potential as a therapy to prevent transplant rejection and autoimmune damage, several strategies are under development to generate tolDCs, in order to avoid activation and expansion of self-reactive T cells. In this article, we summarize the current knowledge relative to the main features of tolDCs, their mechanisms of action and their therapeutic use for autoimmune diseases. Based on the literature reviewed, autologous antigen-specific tolDCs might constitute a promising strategy to suppress autoreactive T cells and reduce detrimental inflammatory processes. • Tolerogenic dendritic cells exhibit a stable immature or semi-mature phenotype. • Generation of tolerogenic dendritic cells is associated to inhibitory checkpoint molecules expression. • Therapeutic administration of tolerogenic dendritic cells loaded with disease-relevant antigens induces specific tolerance. [ABSTRACT FROM AUTHOR]