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 Estes, Jason M. Brenchley

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Article number3967
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Mudd, J. C., Busman-Sahay, K., DiNapoli, S. R., Lai, S., Sheik, V., Lisco, A., Deleage, C., Richardson, B., Palesch, D. J., Paiardini, M., Cameron, M., Sereti, I., Reeves, R. K., Estes, J., & Brenchley, J. M. (2018). Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells. Nature Communications, 9(1), [3967]. https://doi.org/10.1038/s41467-018-05528-3