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 af dette arbejde

86 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Immunity
Vol/bind	44
Udgave nummer	2
Sider (fra-til)	391-405
Antal sider	15
ISSN	1074-7613
DOI	https://doi.org/10.1016/j.immuni.2016.01.006
Status	Udgivet - 16 feb. 2016

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http://www.cell.com/article/S1074761316000303/pdf

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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, bind 44, nr. 2, s. 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.",

keywords = "HIV-infection, Innate lymphoid cells",

author = "Kl{\o}verpris, {Henrik N.} and Kazer, {Samuel W.} and Jenny Mj{\"o}sberg and Mabuka, {Jenniffer M.} and Amanda Wellmann and Zaza Ndhlovu and Yadon, {Marisa C.} and Shepherd Nhamoyebonde and Maximilian Muenchhoff and Yannick Simoni and Frank Andersson and Warren Kuhn and Nigel Garrett and Burgers, {Wendy A.} and Philomena Kamya and Karyn Pretorius and Krista Dong and Amber Moodley and Newell, {Evan W.} and Victoria Kasprowicz and {Abdool Karim}, {Salim S.} and Philip Goulder and Shalek, {Alex K.} and Walker, {Bruce D.} and Thumbi Ndung'u and Alasdair Leslie",

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doi = "10.1016/j.immuni.2016.01.006",

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T1 - Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-Infection in the Absence of Viral Suppression

AU - Kløverpris, Henrik N.

AU - Kazer, Samuel W.

AU - Mjösberg, Jenny

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

PY - 2016/2/16

Y1 - 2016/2/16

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.

KW - HIV-infection

KW - Innate lymphoid cells

U2 - 10.1016/j.immuni.2016.01.006

DO - 10.1016/j.immuni.2016.01.006

M3 - Journal article

C2 - 26850658

AN - SCOPUS:84958108976

SN - 1074-7613

VL - 44

SP - 391

EP - 405

JO - Immunity

JF - Immunity

IS - 2

ER -

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

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