9 results on '"Francesca Caccuri"'
Search Results
2. TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
- Author
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Daria Bortolotti, Valentina Gentili, Sabrina Rizzo, Giovanna Schiuma, Silvia Beltrami, Giovanni Strazzabosco, Mercedes Fernandez, Francesca Caccuri, Arnaldo Caruso, and Roberta Rizzo
- Subjects
SARS-CoV-2 ,TLR ,RNA sensors ,Biology (General) ,QH301-705.5 - Abstract
(1) Background: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the coronavirus disease (COVID-19) that has led to a pandemic that began in March 2020. The role of the SARS-CoV-2 components on innate and adaptive immunity is still unknown. We investigated the possible implication of pathogen-associated molecular patterns (PAMPs)–pattern recognition receptors (PRRs) interaction. (2) Methods: We infected Calu-3/MRC-5 multicellular spheroids (MTCSs) with a SARS-CoV-2 clinical strain and evaluated the activation of RNA sensors, transcription factors, and cytokines/interferons (IFN) secretion, by quantitative real-time PCR, immunofluorescence, and ELISA. (3) Results: Our results showed that the SARS-CoV-2 infection of Calu-3/MRC-5 multicellular spheroids induced the activation of the TLR3 and TLR7 RNA sensor pathways. In particular, TLR3 might act via IRF3, producing interleukin (IL)-1α, IL-1β, IL-4, IL-6, and IFN-α and IFN-β, during the first 24 h post-infection. Then, TLR3 activates the NFκB transduction pathway, leading to pro-inflammatory cytokine secretion. Conversely, TLR7 seems to mainly act via NFκB, inducing type 1 IFN, IFN-γ, and IFN-λ3, starting from the 48 h post-infection. (4) Conclusion: We showed that both TLR3 and TLR7 are involved in the control of innate immunity during lung SARS-CoV-2 infection. The activation of TLRs induced pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-4, and IL-6, as well as interferons. TLRs could be a potential target in controlling the infection in the early stages of the disease.
- Published
- 2021
- Full Text
- View/download PDF
3. SARS-CoV-2 Infection Remodels the Phenotype and Promotes Angiogenesis of Primary Human Lung Endothelial Cells
- Author
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Francesca Caccuri, Antonella Bugatti, Alberto Zani, Antonella De Palma, Dario Di Silvestre, Ekta Manocha, Federica Filippini, Serena Messali, Paola Chiodelli, Giovanni Campisi, Simona Fiorentini, Fabio Facchetti, Pierluigi Mauri, and Arnaldo Caruso
- Subjects
COVID-19 ,endothelial cell dysfunction ,infection ,angiogenesis ,proteome ,Biology (General) ,QH301-705.5 - Abstract
SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) and acute lung injury are life-threatening manifestations of severe viral infection. The pathogenic mechanisms that lead to respiratory complications, such as endothelialitis, intussusceptive angiogenesis, and vascular leakage remain unclear. In this study, by using an immunofluorescence assay and in situ RNA-hybridization, we demonstrate the capability of SARS-CoV-2 to infect human primary lung microvascular endothelial cells (HL-mECs) in the absence of cytopathic effects and release of infectious particles. Preliminary data point to the role of integrins in SARS-CoV-2 entry into HL-mECs in the absence of detectable ACE2 expression. Following infection, HL-mECs were found to release a plethora of pro-inflammatory and pro-angiogenic molecules, as assessed by microarray analyses. This conditioned microenvironment stimulated HL-mECs to acquire an angiogenic phenotype. Proteome analysis confirmed a remodeling of SARS-CoV-2-infected HL-mECs to inflammatory and angiogenic responses and highlighted the expression of antiviral molecules as annexin A6 and MX1. These results support the hypothesis of a direct role of SARS-CoV-2-infected HL-mECs in sustaining vascular dysfunction during the early phases of infection. The construction of virus-host interactomes will be instrumental to identify potential therapeutic targets for COVID-19 aimed to inhibit HL-mEC-sustained inflammation and angiogenesis upon SARS-CoV-2 infection.
- Published
- 2021
- Full Text
- View/download PDF
4. Serological Response to SARS-CoV-2 in Health Care Workers Employed in a Large Tertiary Hospital in Lombardy, Northern Italy
- Author
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Agnese Comelli, Emanuele Focà, Emanuele Sansone, Cesare Tomasi, Elisa Albini, Eugenia Quiros-Roldan, Lina Rachele Tomasoni, Emma Sala, Carlo Bonfanti, Francesca Caccuri, Arnaldo Caruso, Giuseppe De Palma, and Francesco Castelli
- Subjects
SARS-CoV-2 infection ,health care workers ,COVID-19 ,seroprevalence ,Biology (General) ,QH301-705.5 - Abstract
Background: COVID-19 pandemic is requesting unprecedented efforts by health-care workers (HCWs) in all countries, and especially in Italy during the first semester of 2020. Methods: This is a retrospective, observational study conducted at the Spedali Civili General Hospital, in Brescia, Northern Italy during the SARS CoV-2 pandemic in the first semester of 2020. Serum samples from HCWs were tested for SARS-CoV-2 spike protein-specific antibodies. An online survey was used to collect demographic, clinical, and epidemiological data. Results: Of the 1893 HCWs included, 433 (22.9%) were found seropositive for SARS-CoV-2 IgG. The cumulative prevalence of SARS-CoV-2 infection (antibodies production or past positive RT-PCR on nasal/throat swab) was 25.1% (475/1893). Fifty-six out of 433 (13%) seropositive participants declared to have been asymptomatic during the study period. The development of COVID-19 signs or symptoms is the main determinant of seropositivity (OR: 11.3, p < 0.0001) along with their duration and severity. 40/290 (14.5%) HCWs with documented positive RT-PCR during the study period did not show any detectable antibody response. IgG levels positively correlate with age, COVID-19-compatible signs and symptoms experienced and their duration. Conclusions: In this study, carried out in one of the most affected areas in Europe, we demonstrate that most HCWs with COVID-19 related symptoms develop a spike protein-specific antibodies with potential neutralizing effect.
- Published
- 2021
- Full Text
- View/download PDF
5. Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response
- Author
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Antonella Bugatti, Stefania Marsico, Manuela Fogli, Sara Roversi, Serena Messali, Daniela Bosisio, Cinzia Giagulli, Arnaldo Caruso, Silvano Sozzani, Simona Fiorentini, and Francesca Caccuri
- Subjects
human metapneumovirus ,dendritic cells ,Th2 response ,IL-4 ,OX40L ,Biology (General) ,QH301-705.5 - Abstract
Human Metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, per se, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment.
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- 2020
- Full Text
- View/download PDF
6. Prevalence of Non-B HIV-1 Subtypes in North Italy and Analysis of Transmission Clusters Based on Sequence Data Analysis
- Author
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Giovanni Lorenzin, Franco Gargiulo, Arnaldo Caruso, Francesca Caccuri, Emanuele Focà, Anna Celotti, Eugenia Quiros-Roldan, Ilaria Izzo, Francesco Castelli, and Maria A. De Francesco
- Subjects
clusters ,hiv ,phylogeny ,subtypes ,epidemic ,Biology (General) ,QH301-705.5 - Abstract
HIV-1 diversity is increasing in European countries due to immigration flows, as well as travels and human mobility, leading to the circulation of both new viral subtypes and new recombinant forms, with important implications for public health. We analyzed 710 HIV-1 sequences comprising protease and reverse-transcriptase (PR/RT) coding regions, sampled from 2011 to 2017, from naive patients in Spedali Civili Hospital, Brescia, Italy. Subtyping was performed by using a combination of different tools; the phylogenetic analysis with a structured coalescence model and Makarov Chain Monte Carlo was used on the datasets, to determine clusters and evolution. We detected 304 (43%) patients infected with HIV-1 non-B variants, of which only 293 sequences were available, with four pure subtypes and five recombinant forms; subtype F1 (17%) and CRF02_AG (51.1%) were most common. Twenty-five transmission clusters were identified, three of which included >10 patients, belonging to subtype CRF02_AG and subtype F. Most cases of alleged transmission were between heterosexual couples. Probably due to strong migratory flows, we have identified different subtypes with particular patterns of recombination or, as in the case of the subtype G (18/293, 6.1%), to a complete lack of relationship between the sequenced strains, revealing that they are all singletons. Continued HIV molecular surveillance is most important to analyze the dynamics of the boost of transmission clusters in order to implement public health interventions aimed at controlling the HIV epidemic.
- Published
- 2019
- Full Text
- View/download PDF
7. TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
- Author
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Roberta Rizzo, Francesca Caccuri, Sabrina Rizzo, Valentina Gentili, Silvia Beltrami, Daria Bortolotti, M. Fernandez, Giovanni Strazzabosco, Giovanna Schiuma, and Arnaldo Caruso
- Subjects
Microbiology (medical) ,QH301-705.5 ,viruses ,Biology ,medicine.disease_cause ,Microbiology ,Article ,NO ,RNA sensors ,Virology ,TLR ,medicine ,Biology (General) ,Transcription factor ,Coronavirus ,Innate immune system ,SARS-CoV-2 ,virus diseases ,TLR7 ,Acquired immune system ,Immunology ,TLR3 ,Cytokine secretion ,IRF3 - Abstract
(1) Background: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the coronavirus disease (COVID-19) that has led to a pandemic that began in March 2020. The role of the SARS-CoV-2 components on innate and adaptive immunity is still unknown. We investigated the possible implication of pathogen-associated molecular patterns (PAMPs)–pattern recognition receptors (PRRs) interaction. (2) Methods: We infected Calu-3/MRC-5 multicellular spheroids (MTCSs) with a SARS-CoV-2 clinical strain and evaluated the activation of RNA sensors, transcription factors, and cytokines/interferons (IFN) secretion, by quantitative real-time PCR, immunofluorescence, and ELISA. (3) Results: Our results showed that the SARS-CoV-2 infection of Calu-3/MRC-5 multicellular spheroids induced the activation of the TLR3 and TLR7 RNA sensor pathways. In particular, TLR3 might act via IRF3, producing interleukin (IL)-1α, IL-1β, IL-4, IL-6, and IFN-α and IFN-β, during the first 24 h post-infection. Then, TLR3 activates the NFκB transduction pathway, leading to pro-inflammatory cytokine secretion. Conversely, TLR7 seems to mainly act via NFκB, inducing type 1 IFN, IFN-γ, and IFN-λ3, starting from the 48 h post-infection. (4) Conclusion: We showed that both TLR3 and TLR7 are involved in the control of innate immunity during lung SARS-CoV-2 infection. The activation of TLRs induced pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-4, and IL-6, as well as interferons. TLRs could be a potential target in controlling the infection in the early stages of the disease.
- Published
- 2021
8. Serological Response to SARS-CoV-2 in Health Care Workers Employed in a Large Tertiary Hospital in Lombardy, Northern Italy
- Author
-
Emanuele Focà, Cesare Tomasi, Eugenia Quiros-Roldan, Emma Sala, Arnaldo Caruso, Elisa Albini, Lina Rachele Tomasoni, Francesca Caccuri, Carlo Bonfanti, Francesco Castelli, Emanuele Sansone, Agnese Comelli, and Giuseppe De Palma
- Subjects
0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Microbiology ,Asymptomatic ,Article ,health care workers ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Internal medicine ,Pandemic ,Epidemiology ,Health care ,Medicine ,Seroprevalence ,030212 general & internal medicine ,COVID-19 ,SARS-CoV-2 infection ,seroprevalence ,lcsh:QH301-705.5 ,business.industry ,virus diseases ,030104 developmental biology ,lcsh:Biology (General) ,Health care workers ,Observational study ,medicine.symptom ,business - Abstract
Background: COVID-19 pandemic is requesting unprecedented efforts by health-care workers (HCWs) in all countries, and especially in Italy during the first semester of 2020. Methods: This is a retrospective, observational study conducted at the Spedali Civili General Hospital, in Brescia, Northern Italy during the SARS CoV-2 pandemic in the first semester of 2020. Serum samples from HCWs were tested for SARS-CoV-2 spike protein-specific antibodies. An online survey was used to collect demographic, clinical, and epidemiological data. Results: Of the 1893 HCWs included, 433 (22.9%) were found seropositive for SARS-CoV-2 IgG. The cumulative prevalence of SARS-CoV-2 infection (antibodies production or past positive RT-PCR on nasal/throat swab) was 25.1% (475/1893). Fifty-six out of 433 (13%) seropositive participants declared to have been asymptomatic during the study period. The development of COVID-19 signs or symptoms is the main determinant of seropositivity (OR: 11.3, p <, 0.0001) along with their duration and severity. 40/290 (14.5%) HCWs with documented positive RT-PCR during the study period did not show any detectable antibody response. IgG levels positively correlate with age, COVID-19-compatible signs and symptoms experienced and their duration. Conclusions: In this study, carried out in one of the most affected areas in Europe, we demonstrate that most HCWs with COVID-19 related symptoms develop a spike protein-specific antibodies with potential neutralizing effect.
- Published
- 2021
9. Prevalence of Non-B HIV-1 Subtypes in North Italy and Analysis of Transmission Clusters Based on Sequence Data Analysis
- Author
-
Emanuele Focà, Giovanni Lorenzin, Francesca Caccuri, Franco Gargiulo, Eugenia Quiros-Roldan, Ilaria Izzo, Maria Antonia De Francesco, Arnaldo Caruso, Francesco Castelli, and Anna Celotti
- Subjects
0301 basic medicine ,Microbiology (medical) ,Hiv epidemic ,Human immunodeficiency virus (HIV) ,hiv ,Biology ,medicine.disease_cause ,phylogeny ,Clusters ,Epidemic ,HIV ,Phylogeny ,Subtypes ,Microbiology ,Article ,epidemic ,Therapy naive ,03 medical and health sciences ,0302 clinical medicine ,Data sequences ,Phylogenetics ,Virology ,medicine ,Coding region ,030212 general & internal medicine ,clusters ,lcsh:QH301-705.5 ,Genetics ,Phylogenetic tree ,subtypes ,Subtyping ,030104 developmental biology ,lcsh:Biology (General) - Abstract
HIV-1 diversity is increasing in European countries due to immigration flows, as well as travels and human mobility, leading to the circulation of both new viral subtypes and new recombinant forms, with important implications for public health. We analyzed 710 HIV-1 sequences comprising protease and reverse-transcriptase (PR/RT) coding regions, sampled from 2011 to 2017, from naive patients in Spedali Civili Hospital, Brescia, Italy. Subtyping was performed by using a combination of different tools, the phylogenetic analysis with a structured coalescence model and Makarov Chain Monte Carlo was used on the datasets, to determine clusters and evolution. We detected 304 (43%) patients infected with HIV-1 non-B variants, of which only 293 sequences were available, with four pure subtypes and five recombinant forms, subtype F1 (17%) and CRF02_AG (51.1%) were most common. Twenty-five transmission clusters were identified, three of which included >, 10 patients, belonging to subtype CRF02_AG and subtype F. Most cases of alleged transmission were between heterosexual couples. Probably due to strong migratory flows, we have identified different subtypes with particular patterns of recombination or, as in the case of the subtype G (18/293, 6.1%), to a complete lack of relationship between the sequenced strains, revealing that they are all singletons. Continued HIV molecular surveillance is most important to analyze the dynamics of the boost of transmission clusters in order to implement public health interventions aimed at controlling the HIV epidemic.
- Published
- 2019
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