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

Author

Listed:
  • Joseph C. Mudd

    (National Institutes of Health)

  • Kathleen Busman-Sahay

    (Leidos Biomedical Research, Inc
    Oregon Health and Science University (OHSU))

  • Sarah R. DiNapoli

    (National Institutes of Health)

  • Stephen Lai

    (National Institutes of Health)

  • Virginia Sheik

    (Food and Drug Administration)

  • Andrea Lisco

    (National Institutes of Health)

  • Claire Deleage

    (Leidos Biomedical Research, Inc)

  • Brian Richardson

    (Case Western Reserve University)

  • David J. Palesch

    (Emory University)

  • Mirko Paiardini

    (Emory University)

  • Mark Cameron

    (Case Western Reserve University)

  • Irini Sereti

    (National Institutes of Health)

  • R. Keith Reeves

    (Harvard Medical School)

  • Jacob D. Estes

    (Leidos Biomedical Research, Inc
    Oregon Health and Science University (OHSU))

  • Jason M. Brenchley

    (National Institutes of Health)

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.

Suggested Citation

  • 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, 2018. "Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05528-3
    DOI: 10.1038/s41467-018-05528-3
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