PMID- 32675560 OWN - NLM STAT- MEDLINE DCOM- 20210218 LR - 20210218 IS - 1473-5571 (Electronic) IS - 0269-9370 (Linking) VI - 34 IP - 10 DP - 2020 Aug 1 TI - High abundance of genus Prevotella is associated with dysregulation of IFN-I and T cell response in HIV-1-infected patients. PG - 1467-1473 LID - 10.1097/QAD.0000000000002574 [doi] AB - OBJECTIVE: HIV-1-associated dysbiosis is most commonly characterized by overall decreased diversity, with abundance of the genus Prevotella, recently related to inflammatory responses. DESIGN: A pilot study including 10 antiretroviral therapy-treated HIV-1-infected men and 50 uninfected controls was performed to identify the main gut dysbiosis determinants (e.g. Prevotella enrichment), that may affect mucosal antiviral defenses and T cell immunity in HIV-1-infected individuals. METHODS: 16rRNA gene sequencing was applied to the HIV-1-infected individuals' fecal microbiota and compared with controls. Measurements of CD4 and CD8 T cell activation [CD38, human leukocyte antigen (HLA)-DR, CD38 HLA-DR] and frequencies of Th17, obtained from lamina propria lymphocytes isolated from five different intestinal sites, were performed by flow cytometry. IFNbeta, IFNAR1 and MxA gene expression level was evaluated by real-time PCR in lamina propria lymphocytes. Nonparametric t tests were used for statistical analysis. RESULTS: HIV-1-infected men had a significant fecal microbial communities' imbalance, including different levels of genera Faecalibacterium, Prevotella, Alistipes and Bacteroides, compared with controls. Notably, Prevotella abundance positively correlated with frequencies of CD4 T cells expressing CD38 or HLA-DR and coexpressing CD38 and HLA-DR (P < 0.05 for all these measures). The same trend was observed for the activated CD8 T cells. Moreover, Prevotella levels were inversely correlated with IFN-I genes (P < 0.05 for IFNbeta, IFNAR1 and MxA genes) and the frequencies of Th17 cells (P < 0.05). By contrast, no statistically significant correlations were observed for the remaining bacterial genera. CONCLUSION: Our findings suggest that Prevotella enrichment might affect gut mucosal IFN-I pathways and T cell response in HIV-1-infected patients, thus contributing to immune dysfunction. FAU - Pinacchio, Claudia AU - Pinacchio C AD - Department of Public Health and Infectious Diseases. FAU - Scagnolari, Carolina AU - Scagnolari C AD - Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome. FAU - Iebba, Valerio AU - Iebba V AD - Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo'. AD - Department of Medical Sciences, University of Trieste, Trieste. FAU - Santinelli, Letizia AU - Santinelli L AD - Department of Public Health and Infectious Diseases. FAU - Innocenti, Giuseppe P AU - Innocenti GP AD - Department of Public Health and Infectious Diseases. FAU - Frasca, Federica AU - Frasca F AD - Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome. FAU - Bitossi, Camilla AU - Bitossi C AD - Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome. FAU - Scordio, Mirko AU - Scordio M AD - Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome. FAU - Oliveto, Giuseppe AU - Oliveto G AD - Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome. FAU - Ceccarelli, Giancarlo AU - Ceccarelli G AD - Department of Public Health and Infectious Diseases. FAU - Antonelli, Guido AU - Antonelli G AD - Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome. AD - Microbiology and Virology Unit, Sapienza University, Hospital Policlinico Umberto I, Rome, Italy. FAU - Mastroianni, Claudio Maria AU - Mastroianni CM AD - Department of Public Health and Infectious Diseases. FAU - d'Ettorre, Gabriella AU - d'Ettorre G AD - Department of Public Health and Infectious Diseases. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - AIDS JT - AIDS (London, England) JID - 8710219 RN - 0 (HLA-DR Antigens) RN - 0 (IFNAR1 protein, human) RN - 0 (MX1 protein, human) RN - 0 (Myxovirus Resistance Proteins) RN - 156986-95-7 (Receptor, Interferon alpha-beta) RN - 77238-31-4 (Interferon-beta) RN - EC 3.2.2.6 (ADP-ribosyl Cyclase 1) SB - IM MH - ADP-ribosyl Cyclase 1 MH - Adult MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Case-Control Studies MH - Dysbiosis/*immunology MH - HIV Infections/*immunology/microbiology MH - HIV-1 MH - HLA-DR Antigens MH - Humans MH - Interferon-beta/immunology MH - Lymphocyte Activation MH - Male MH - Middle Aged MH - Myxovirus Resistance Proteins/immunology MH - Pilot Projects MH - Prevotella/*isolation & purification MH - Receptor, Interferon alpha-beta/immunology EDAT- 2020/07/18 06:00 MHDA- 2021/02/20 06:00 CRDT- 2020/07/18 06:00 PHST- 2020/07/18 06:00 [entrez] PHST- 2020/07/18 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] AID - 00002030-202008010-00005 [pii] AID - 10.1097/QAD.0000000000002574 [doi] PST - ppublish SO - AIDS. 2020 Aug 1;34(10):1467-1473. doi: 10.1097/QAD.0000000000002574.