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

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

Author information

1
Barrier Immunity Section, Lab of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive, Bethesda, MD, 20892, USA.
2
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, 8560 Progress Drive, Frederick, MD, 21701, USA.
3
Vaccine and Gene Therapy Institute and Oregon National Primate Research Center (ONPRC), Oregon Health and Science University (OHSU), 505N.W. 185th Avenue, Beaverton, OR, 97006, USA.
4
Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Avenue, Silver Spring, MD, 20903, USA.
5
Clinical and Molecular Retrovirology Section/Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA.
6
Department of Epidemiology and Biostatistics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
7
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA.
8
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
9
Barrier Immunity Section, Lab of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive, Bethesda, MD, 20892, USA. jbrenchl@niaid.nih.gov.

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.

PMID:
30262807
PMCID:
PMC6160474
DOI:
10.1038/s41467-018-05528-3
[Indexed for MEDLINE]
Free PMC Article

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