Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-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-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 KasprowiczSalim S. Abdool Karim, Philip Goulder, Alex K. Shalek, Bruce D. Walker, Thumbi Ndung'u, Alasdair Leslie

^*Corresponding author for this work

86 Citations (Scopus)

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-on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-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-infection, lymphoid tissue breakdown, and persistent immune dysfunction.

Original language	English
Journal	Immunity
Volume	44
Issue number	2
Pages (from-to)	391-405
Number of pages	15
ISSN	1074-7613
DOIs	https://doi.org/10.1016/j.immuni.2016.01.006
Publication status	Published - 16 Feb 2016

Keywords

HIV-infection
Innate lymphoid cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Kløverpris, H. N., Kazer, S. W., Mjösberg, J., Mabuka, J. M., Wellmann, A., Ndhlovu, Z., Yadon, M. C., Nhamoyebonde, S., Muenchhoff, M., Simoni, Y., Andersson, F., Kuhn, W., Garrett, N., Burgers, W. A., Kamya, P., Pretorius, K., Dong, K., Moodley, A., Newell, E. W., ... Leslie, A. (2016). Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-Infection in the Absence of Viral Suppression. Immunity, 44(2), 391-405. https://doi.org/10.1016/j.immuni.2016.01.006

Kløverpris, HN, Kazer, SW, Mjösberg, J, Mabuka, JM, Wellmann, A, Ndhlovu, Z, Yadon, MC, Nhamoyebonde, S, Muenchhoff, M, Simoni, Y, Andersson, F, Kuhn, W, Garrett, N, Burgers, WA, Kamya, P, Pretorius, K, Dong, K, Moodley, A, Newell, EW, Kasprowicz, V, Abdool Karim, SS, Goulder, P, Shalek, AK, Walker, BD, Ndung'u, T & Leslie, A 2016, 'Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-Infection in the Absence of Viral Suppression', Immunity, vol. 44, no. 2, pp. 391-405. https://doi.org/10.1016/j.immuni.2016.01.006

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title = "Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-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-on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-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-infection, lymphoid tissue breakdown, and persistent immune dysfunction.",

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AU - Kløverpris, Henrik N.

AU - Kazer, Samuel W.

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AU - Mabuka, Jenniffer M.

AU - Wellmann, Amanda

AU - Ndhlovu, Zaza

AU - Yadon, Marisa C.

AU - Nhamoyebonde, Shepherd

AU - Muenchhoff, Maximilian

AU - Simoni, Yannick

AU - Andersson, Frank

AU - Kuhn, Warren

AU - Garrett, Nigel

AU - Burgers, Wendy A.

AU - Kamya, Philomena

AU - Pretorius, Karyn

AU - Dong, Krista

AU - Moodley, Amber

AU - Newell, Evan W.

AU - Kasprowicz, Victoria

AU - Abdool Karim, Salim S.

AU - Goulder, Philip

AU - Shalek, Alex K.

AU - Walker, Bruce D.

AU - Ndung'u, Thumbi

AU - Leslie, Alasdair

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N2 - 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-on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-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-infection, lymphoid tissue breakdown, and persistent immune dysfunction.

AB - 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-on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-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-infection, lymphoid tissue breakdown, and persistent immune dysfunction.

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KW - Innate lymphoid cells

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

Abstract

Keywords

UN SDGs

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