Enteric mucosa integrity in the presence of a preserved innate interleukin 22 compartment in HIV type 1-treated individuals

J Infect Dis. 2014 Aug 15;210(4):630-40. doi: 10.1093/infdis/jiu126. Epub 2014 Mar 5.

Abstract

Background: Interleukin 22 (IL-22) is emerging as a key cytokine for gut epithelial homeostasis and mucosal repair. Gut disruption is a hallmark of human immunodeficiency virus (HIV) infection. Here, we investigated IL-22 production and gut mucosal integrity in HIV type 1 (HIV-1)-infected individuals receiving long-term antiretroviral therapy (ART).

Methods: Biopsy specimens from 37 individuals who underwent colonoscopy primarily for cancer screening and from 17 HIV-1-infected and 20 healthy age-matched controls were assessed.

Results: We found significant depletion of sigmoid IL-22-producing CD4(+) T cells (T-helper type 22 [Th22] cells) even after prolonged ART, contrasting with the apparently normal compartments of regulatory and interleukin 17 (IL-17)-producing CD4(+) T cells, as well as total mucosal CD4(+) T cells. Despite the preferential Th22 cell depletion, IL-22 production by innate lymphoid cells (ILCs) was similar to that observed in HIV-1-seronegative subjects, and transcription of genes encoding molecules relevant for IL-22 production (ie, AHR, IL23, IL23R, IL1B, IL6, and TGFB1) was preserved. Remarkably, levels of transcripts of IL-22-target genes (ie, REG3G, DEFB4A, S100A9, MUC1, and MUC13) were unaltered, suggesting an adequate production of antimicrobial peptides and mucins. In agreement, enteric epithelial architecture was fully preserved.

Conclusions: Despite the reduced Th22 cell subset, innate IL-22-mediated mechanisms, essential for sigmoid mucosa integrity, were fully operational in long-term-treated HIV-1-infected individuals. Our data highlight IL-22 production by ILCs as an important target for therapies aimed at facilitating human mucosal reconstitution.

Keywords: HIV/AIDS; IL-22; antiretroviral therapy; gut associated lymphoid tissue; mucosa reconstitution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiretroviral Therapy, Highly Active / methods
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunity, Innate / immunology*
  • Interleukins / immunology*
  • Intestinal Mucosa / immunology*
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Transcription, Genetic / immunology

Substances

  • Interleukins
  • interleukin-22