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

Joseph C Mudd | Kathleen Busman-Sahay | Sarah R DiNapoli | Stephen Lai | Virginia Sheik | Andrea Lisco | Claire Deleage | Brian Richardson | David J Palesch | Mirko Paiardini | Mark Cameron | Irini Sereti | R Keith Reeves | Jacob D Estes | Jason M Brenchley
Nature communications | 2018

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.

Pubmed ID: 30262807

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI116379
  • Agency: NIH HHS, United States
    Id: P51 OD011132
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE026327
  • Agency: CCR NIH HHS, United States
    Id: HHSN261200800001C
  • Agency: NIH HHS, United States
    Id: U42 OD011023
  • Agency: NCI NIH HHS, United States
    Id: HHSN261200800001E
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI036219

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