Hallmarks of Primate Lentiviral Immunodeficiency Infection Recapitulate Loss of Innate Lymphoid Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Sep 29

PMID 30262807

Citations 25

Authors

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

Affiliations

Soon will be listed here.

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.

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References

Estes J, Harris L, Klatt N, Tabb B, Pittaluga S, Paiardini M . Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 2010; 6(8):e1001052. PMC: 2924359. DOI: 10.1371/journal.ppat.1001052. View

Pandrea I, Gautam R, Ribeiro R, Brenchley J, Butler I, Pattison M . Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol. 2007; 179(5):3035-46. PMC: 2367134. DOI: 10.4049/jimmunol.179.5.3035. View

Sandler N, Wand H, Roque A, Law M, Nason M, Nixon D . Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011; 203(6):780-90. PMC: 3071127. DOI: 10.1093/infdis/jiq118. View

Lederman M, Funderburg N, Sekaly R, Klatt N, Hunt P . Residual immune dysregulation syndrome in treated HIV infection. Adv Immunol. 2013; 119:51-83. PMC: 4126613. DOI: 10.1016/B978-0-12-407707-2.00002-3. View

Goldstein S, Elkins W, London W, Hahn A, Goeken R, Martin J . Immunization with whole inactivated vaccine protects from infection by SIV grown in human but not macaque cells. J Med Primatol. 1994; 23(2-3):75-82. DOI: 10.1111/j.1600-0684.1994.tb00105.x. View

Klatt N, Estes J, Sun X, Ortiz A, Barber J, Harris L . Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol. 2012; 5(6):646-57. PMC: 3443541. DOI: 10.1038/mi.2012.38. View

Satoh-Takayama N, Lesjean-Pottier S, Vieira P, Sawa S, Eberl G, Vosshenrich C . IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors. J Exp Med. 2010; 207(2):273-80. PMC: 2822619. DOI: 10.1084/jem.20092029. View

Rethi B, Fluur C, Atlas A, Krzyzowska M, Mowafi F, Grutzmeier S . Loss of IL-7Ralpha is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients. AIDS. 2005; 19(18):2077-86. DOI: 10.1097/01.aids.0000189848.75699.0f. View

Zonios D, Sheikh V, Sereti I . Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T cells. Arthritis Res Ther. 2012; 14(4):222. PMC: 3580591. DOI: 10.1186/ar4027. View

10.

Barouch D, Ghneim K, Bosche W, Li Y, Berkemeier B, Hull M . Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys. Cell. 2016; 165(3):656-67. PMC: 4842119. DOI: 10.1016/j.cell.2016.03.021. View

11.

Xu H, Wang X, Liu D, Moroney-Rasmussen T, Lackner A, Veazey R . IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. Mucosal Immunol. 2012; 5(6):658-69. PMC: 3702374. DOI: 10.1038/mi.2012.39. View

12.

Hao X, Lucero C, Turkbey B, Bernardo M, Morcock D, Deleage C . Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. Nat Commun. 2015; 6:8020. PMC: 4544774. DOI: 10.1038/ncomms9020. View

13.

Macal M, Sankaran S, Chun T, Reay E, Flamm J, Prindiville T . Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses. Mucosal Immunol. 2008; 1(6):475-88. DOI: 10.1038/mi.2008.35. View

14.

Mattapallil J, Douek D, Hill B, Nishimura Y, Martin M, Roederer M . Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature. 2005; 434(7037):1093-7. DOI: 10.1038/nature03501. View

15.

Hepworth M, Monticelli L, Fung T, Ziegler C, Grunberg S, Sinha R . Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature. 2013; 498(7452):113-7. PMC: 3699860. DOI: 10.1038/nature12240. View

16.

Cupedo T, Crellin N, Papazian N, Rombouts E, Weijer K, Grogan J . Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol. 2008; 10(1):66-74. DOI: 10.1038/ni.1668. View

17.

Bjorklund A, Forkel M, Picelli S, Konya V, Theorell J, Friberg D . The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing. Nat Immunol. 2016; 17(4):451-60. DOI: 10.1038/ni.3368. View

18.

Silver J, Kearley J, Copenhaver A, Sanden C, Mori M, Yu L . Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs. Nat Immunol. 2016; 17(6):626-35. PMC: 5345745. DOI: 10.1038/ni.3443. View

19.

Hazenberg M, Spits H . Human innate lymphoid cells. Blood. 2014; 124(5):700-9. DOI: 10.1182/blood-2013-11-427781. View

20.

Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz J . A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature. 2008; 457(7230):722-5. PMC: 3772687. DOI: 10.1038/nature07537. View