Contribution of Innate Lymphoid Cells in Supplementing Cytokines Produced by CD4+ T Cells During Acute and Chronic SIV Infection of the Colon

Natasha Ferguson, Andrew Cogswell, Edward Barker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

HIV/SIV (simian immunodeficiency virus) infection leads to a loss of CD4+ T helper (Th) cells in number and function that begins during the acute phase and persists through the chronic phase of infection. In particular, there is a drastic decrease of Th17 and Th22 cells in the HIV/SIV-infected gastrointestinal (GI) tract as a source of interleukin (IL)-17 and IL-22. These cytokines are vital in the immune response to extracellular pathogens and maintenance of the GI tract. However, innate lymphoid cells (ILCs) are a source of IL-17 and IL-22 during the early stages of an immune response in mucosal tissue and remain vital cytokine producers when the immune response is persistent. Here, we wanted to determine whether ILCs are a source of IL-17 and IL-22 in the SIV-infected colon and could compensate for the loss of Th17 and Th22 cells. As a control, we evaluated the frequency and number of ILCs expressing interferon-gamma (IFNc) and tumor necrosis factor-alpha (TNFa). We determined the frequency and number of cytokine expressing ILC subsets and T cell subsets within leukocytes from the colons of uninfected as well as acute and chronic SIV-infected colons without in vitro mitogenic stimulation. In the present study, we find that: (1) the frequency of IL-22, IFNc, and TNFa but not IL-17 producing ILCs is increased in the acutely infected colon and remains high during the chronically infected colon relative to cytokine expressing ILCs in the uninfected colon, (2) ILCs are a significant source of IL-22, IFNc, and TNFa but not IL-17 when CD4+ T lymphocytes in the gut lose their capacity to secrete these cytokines during SIV infection, and (3) the changes in the cytokines expressed by ILCs relative to CD4+ T cells in the infected colon were not due to increases in the frequency or number of ILCs in relation to T lymphocytes found in the tissue.

Original languageEnglish (US)
Pages (from-to)709-725
Number of pages17
JournalAIDS research and human retroviruses
Volume38
Issue number9
DOIs
StatePublished - Sep 1 2022

Keywords

  • HIV/SIV pathogenesis
  • acute infection
  • gastrointestinal tract
  • immune response
  • inflammation
  • innate immunity
  • innate lymphoid cells
  • mucosal immunology

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology
  • Immunology

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