title: Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.
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.
authors: 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: henrik.kloverpris@k-rith.org.
authors: Henrik N
authors: HN
authors: Kløverpris
authors: 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.
authors: Samuel W
authors: SW
authors: Kazer
authors: Center for Infectious Medicine, Karolinska Institute, 171 76 Stockholm, Sweden.
authors: Jenny
authors: J
authors: Mjösberg
authors: KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
authors: Jenniffer M
authors: JM
authors: Mabuka
authors: KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
authors: Amanda
authors: A
authors: Wellmann
authors: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa.
authors: Zaza
authors: Z
authors: Ndhlovu
authors: KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
authors: Marisa C
authors: MC
authors: Yadon
authors: KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
authors: Shepherd
authors: S
authors: Nhamoyebonde
authors: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa; Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK.
authors: Maximilian
authors: M
authors: Muenchhoff
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138632 Singapore, Singapore.
authors: Yannick
authors: Y
authors: Simoni
authors: Department of Surgery, Inkosi Albert Luthuli Hospital, KwaZulu-Natal, 4058 Durban, South Africa.
authors: Frank
authors: F
authors: Andersson
authors: ENT department Stanger Hospital, Stanger, KwaZulu Natal, 4450 Durban, South Africa.
authors: Warren
authors: W
authors: Kuhn
authors: Department of Infectious Diseases, UKZN, 4001 Durban, South Africa; Center for the AIDS Programme of Research in South Africa - CAPRISA, 4001 Durban, South Africa.
authors: Nigel
authors: N
authors: Garrett
authors: Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 7925 Cape Town, South Africa.
authors: Wendy A
authors: WA
authors: Burgers
authors: 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.
authors: Philomena
authors: P
authors: Kamya
authors: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa.
authors: Karyn
authors: K
authors: Pretorius
authors: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA.
authors: Krista
authors: K
authors: Dong
authors: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA.
authors: Amber
authors: A
authors: Moodley
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138632 Singapore, Singapore.
authors: Evan W
authors: EW
authors: Newell
authors: KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
authors: Victoria
authors: V
authors: Kasprowicz
authors: 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.
authors: Salim S
authors: SS
authors: Abdool Karim
authors: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, UKZN, 4001 Durban, South Africa; Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK.
authors: Philip
authors: P
authors: Goulder
authors: 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.
authors: Alex K
authors: AK
authors: Shalek
authors: 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.
authors: Bruce D
authors: BD
authors: Walker
authors: 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.
authors: Thumbi
authors: T
authors: Ndung'u
authors: 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.
authors: Alasdair
authors: A
authors: Leslie
mesh_terms: D000208:Acute Disease; D000998:Antiviral Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement; D002478:Cells, Cultured; D002908:Chronic Disease; D015331:Cohort Studies; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000473:pathology* / Q000821:virology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D007371:Interferon-gamma
keywords: HIV-1 infection; innate lymphoid cells