High abundance of genus Prevotella is associated with dysregulation of IFN-I and T cell response in HIV-1-infected patients.

Objective: HIV-1-associated dysbiosis is most commonly characterized by overall decreased diversity, with abundance of the genusPrevotella,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.Prevotellaenrichment), that may affect mucosal antiviral defenses and T cell immunity in HIV-1-infected individuals. Methods: 16rRNAgene 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.IFN beta,IFNAR1andMxAgene expression level was evaluated by real-time PCR in lamina propria lymphocytes. Nonparametricttests were used for statistical analysis. Results: HIV-1-infected men had a significant fecal microbial communities' imbalance, including different levels of generaFaecalibacterium, Prevotella, AlistipesandBacteroides,compared with controls. Notably,Prevotellaabundance 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,Prevotellalevels were inversely correlated withIFN-Igenes (P IFN beta, IFNAR1andMxAgenes) 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 thatPrevotellaenrichment might affect gut mucosalIFN-Ipathways and T cell response in HIV-1-infected patients, thus contributing to immune dysfunction.