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

• Type of Material: Article
• Authors: Joseph C. Mudd, National Institute of Allergy and Infectious Diseases; Kathleen Busman-Sahay, Leidos Biomedical Research, Inc.; Sarah R. DiNapoli, National Institute of Allergy and Infectious Diseases; Stephen Lai, National Institute of Allergy and Infectious Diseases; Virginia Sheik, Food and Drug Administration; Andrea Lisco, National Institute of Allergy and Infectious Diseases; Claire Deleage, Leidos Biomedical Research, Inc.; Brain Richardson, Case Western Reserve University; David J. Palesch, Emory University; Mirko Paiardini, Emory University; Mark Cameron, Case Western Reserve University; Irini Sereti, National Institute of Allergy and Infectious Diseases; R. Keith Reeves, Harvard Medical School; Jacob D. Estes, Leidos Biomedical Research, Inc.; Jason M. Brenchley, National Institute of Allergy and Infectious Diseases
• Language: English
• Date: 2018-09-27
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2018, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-018-05528-3
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 9
• Issue: 1
• Start Page: 3967
• End Page: 3967
• Grant/Funding Information: Samples procured through the Yerkes Primate Center were funded in by ORIP/OD P51OD011132.; Funding for this study was provided in part by the Division of Intramural Research/NIAID/NIH and federal funds from the National Cancer Institute (NIH Contract HHSN261200800001E), National Institute of Dental and Craniofacial Research (NIH Grant R01 DE026327 to R.K.R.), and NIAID (NIH Grant R01 AI116379 awarded to M.P.).; The content of this publication does not necessarily reflect the views or policies of DHHS, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
• Keywords: SUBSETS; DEPLETION; ANTIRETROVIRAL THERAPY; COMMENSAL BACTERIA; Multidisciplinary Sciences; TISSUES; CD4(+) T-CELLS; Science & Technology - Other Topics; SIV INFECTION; VIRUS; HIV-INFECTION; MACAQUES; Science & Technology
• Research Categories: Health Sciences, Public 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.