Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells

Nat Commun. 2018 Sep 27;9(1):3967. doi: 10.1038/s41467-018-05528-3.

Abstract

Innate lymphoid cells (ILCs) play critical roles in mucosal barrier defense and tissue homeostasis. While ILCs are depleted in HIV-1 infection, this phenomenon is not a generalized feature of all viral infections. Here we show in untreated SIV-infected rhesus macaques (RMs) that ILC3s are lost rapidly in mesenteric lymph nodes (MLNs), yet preserved in SIV+ RMs with pharmacologic or natural control of viremia. In healthy uninfected RMs, experimental depletion of CD4+ T cells in combination with dextran sodium sulfate (DSS) is sufficient to reduce ILC frequencies in the MLN. In this setting and in chronic SIV+ RMs, IL-7Rα chain expression diminishes on ILC3s in contrast to the IL-18Rα chain expression which remains stable. In HIV-uninfected patients with durable CD4+ T cell deficiency (deemed idiopathic CD4+ lymphopenia), similar ILC deficiencies in blood were observed, collectively identifying determinants of ILC homeostasis in primates and potential mechanisms underlying their depletion in HIV/SIV infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Dextran Sulfate
  • HIV-1 / physiology
  • Humans
  • Immunity, Innate*
  • Interferon Type I / metabolism
  • Interleukin-17 / metabolism
  • Lymph Nodes / pathology
  • Lymphocytes / immunology*
  • Macaca mulatta
  • Receptors, Interleukin / metabolism
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / physiology*

Substances

  • Interferon Type I
  • Interleukin-17
  • Receptors, Interleukin
  • Dextran Sulfate