HIV-infected immunological non-responders have colon-restricted gut mucosal immune dysfunction

J Infect Dis. 2020 Nov 20;jiaa714. doi: 10.1093/infdis/jiaa714. Online ahead of print.

Abstract

Background: HIV-infected immunological non-responders (INR) fail to reconstitute their CD4 + T cell pool after initiation of antiretroviral therapy, and their prognosis is inferior to the immunological responders (IR). A prevailing hypothesis is that the INR phenotype is caused by a persistently disrupted mucosal barrier, but assessments of gut mucosal immunology in different anatomical compartments are scarce.

Methods: We investigated circulating markers of mucosal dysfunction, immune activation, mucosal Th17 and Th22 cells, and mucosa-adherent microbiota signatures in gut mucosal specimens from sigmoid colon and terminal ileum of 19 INR and 20 IR in addition to 20 HIV negative individuals.

Results: INR had higher blood levels of the enterocyte damage marker Intestinal fatty acid binding protein (I-FABP) than IR. In gut mucosal biopsies, INR had lower fractions of CD4 + T cells, higher fractions of IL-22, and a tendency to higher fractions of IL-17 producing CD4 + T cells. These findings were all restricted to the colon and correlated to circulating markers of enterocyte damage. There were no observed differences in gut microbial composition between INR and IR.

Conclusion: Restricted to the colon, enterocyte damage and mucosal immune dysfunction play a role for insufficient immune reconstitution in HIV infection independently of the gut microbiota.

Keywords: HIV; gut microbiota; immunological non-responders; mucosal immunology.