Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression

Henrik N Kløverpris; Samuel W Kazer; Jenny Mjösberg; Jenniffer M Mabuka; Amanda Wellmann; Zaza Ndhlovu; Marisa C Yadon; Shepherd Nhamoyebonde; Maximilian Muenchhoff; Yannick Simoni; Frank Andersson; Warren Kuhn; Nigel Garrett; Wendy A Burgers; Philomena Kamya; Karyn Pretorius; Krista Dong; Amber Moodley; Evan W Newell; Victoria Kasprowicz; Salim S Abdool Karim; Philip Goulder; Alex K Shalek; Bruce D Walker; Thumbi Ndung'u; Alasdair Leslie

doi:10.1016/j.immuni.2016.01.006

Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression

Immunity. 2016 Feb 16;44(2):391-405. doi: 10.1016/j.immuni.2016.01.006. Epub 2016 Feb 2.

Authors

Henrik N Kløverpris¹, Samuel W Kazer², Jenny Mjösberg³, Jenniffer M Mabuka⁴, Amanda Wellmann⁴, Zaza Ndhlovu⁵, Marisa C Yadon⁴, Shepherd Nhamoyebonde⁴, Maximilian Muenchhoff⁶, Yannick Simoni⁷, Frank Andersson⁸, Warren Kuhn⁹, Nigel Garrett¹⁰, Wendy A Burgers¹¹, Philomena Kamya¹², Karyn Pretorius⁵, Krista Dong¹³, Amber Moodley¹³, Evan W Newell⁷, Victoria Kasprowicz⁴, Salim S Abdool Karim¹⁴, Philip Goulder⁶, Alex K Shalek¹⁵, Bruce D Walker¹⁶, Thumbi Ndung'u¹⁷, Alasdair Leslie¹⁸

Affiliations

¹ KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa; Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: [email protected].
² Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139-4307, USA.
³ Center for Infectious Medicine, Karolinska Institute, 171 76 Stockholm, Sweden.
⁴ KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
⁵ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa.
⁶ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa; Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK.
⁷ Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138632 Singapore, Singapore.
⁸ Department of Surgery, Inkosi Albert Luthuli Hospital, KwaZulu-Natal, 4058 Durban, South Africa.
⁹ ENT department Stanger Hospital, Stanger, KwaZulu Natal, 4450 Durban, South Africa.
¹⁰ Department of Infectious Diseases, UKZN, 4001 Durban, South Africa; Center for the AIDS Programme of Research in South Africa - CAPRISA, 4001 Durban, South Africa.
¹¹ Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 7925 Cape Town, South Africa.
¹² Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa.
¹³ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA.
¹⁴ Center for the AIDS Programme of Research in South Africa - CAPRISA, 4001 Durban, South Africa; Department of Epidemiology, Columbia University, New York, NY 10027, USA.
¹⁵ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139-4307, USA; Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02138, USA.
¹⁶ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
¹⁷ KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa; Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
¹⁸ KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA.

Abstract

Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction.

Keywords: HIV-1 infection; innate lymphoid cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease
Antiviral Agents / administration & dosage
Apoptosis / drug effects
Apoptosis / genetics
Cell Movement
Cells, Cultured
Chronic Disease
Cohort Studies
Gene Expression Regulation
HIV Infections / drug therapy
HIV Infections / immunology*
HIV-1 / immunology*
Humans
Immunity, Innate
Interferon-gamma / genetics
Interferon-gamma / metabolism*
Intestines / pathology*
Intestines / virology
Lymphocytes / drug effects
Lymphocytes / immunology*
Lymphocytes / virology
Time Factors
Treatment Outcome
Viral Load / drug effects
Viral Load / immunology

Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression

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