Human Immunodeficiency Virus–Infected Immunological Nonresponders Have Colon-Restricted Gut Mucosal Immune Dysfunction. (20th November 2020)

• Record Type: Journal Article
• Authors: Meyer-Myklestad, Malin Holm; Medhus, Asle Wilhelm; Lorvik, Kristina Berg; Seljeflot, Ingebjørg; Hansen, Simen Hyll; Holm, Kristian; Stiksrud, Birgitte; Trøseid, Marius; Hov, Johannes Roksund; Kvale, Dag; Dyrhol-Riise, Anne Margarita; Kummen, Martin; Reikvam, Dag Henrik
• Is Part Of: Journal of infectious diseases. Volume 225:Number 4(2022)
• Page Start: 661
• Page End: 674
• Publication Date: 2020-11-20
• Subjects: HIV -- immunological nonresponders -- mucosal immunology -- gut microbiota; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa714
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Human immunodeficiency virus (HIV)–infected immunological nonresponders (INRs) fail to reconstitute their CD4 + T-cell pool after initiation of antiretroviral therapy, and their prognosis is inferior to that of immunological responders (IRs). 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 INRs and 20 IRs in addition to 20 HIV-negative individuals. Results: INRs had higher blood levels of the enterocyte damage marker intestinal fatty acid–binding protein than IRs. In gut mucosal biopsies, INRs had lower fractions of CD4 + T cells, higher fractions of interleukin 22, and a tendency to higher fractions of interleukin 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 INRs and IRs. Conclusions: Restricted to the colon, enterocyte damage and mucosal immune dysfunction play a role for insufficient immune reconstitution in HIV infection independent of the gut microbiota. Abstract : Immunological nonresponders (INRs) had higher levels of circulating markers of enterocyte damage, which correlated with alterations in colonic mucosal CD4 T-cell function. There were no observed differences in gut microbial composition between INRs and immunological responders.