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

被引:123
作者
Kloverpris, Henrik N. [1 ,2 ]
Kazer, Samuel W. [3 ,4 ,5 ,6 ]
Mjosberg, Jenny [7 ]
Mabuka, Jenniffer M. [1 ]
Wellmann, Amanda [1 ]
Ndhlovu, Zaza [8 ]
Yadon, Marisa C. [1 ]
Nhamoyebonde, Shepherd [1 ]
Muenchhoff, Maximilian [8 ,9 ]
Simoni, Yannick [10 ]
Andersson, Frank [11 ]
Kuhn, Warren [12 ]
Garrett, Nigel [13 ,14 ]
Burgers, Wendy A. [15 ,16 ]
Kamya, Philomena [3 ,8 ]
Pretorius, Karyn [8 ]
Dong, Krista [3 ]
Moodley, Amber [3 ]
Newell, Evan W. [10 ]
Kasprowicz, Victoria [1 ]
Karim, Salim S. Abdool [14 ,17 ]
Goulder, Philip [8 ,9 ]
Shalek, Alex K. [3 ,4 ,5 ,6 ,18 ]
Walker, Bruce D. [3 ,8 ,19 ]
Ndung'u, Thumbi [1 ,3 ,8 ,20 ]
Leslie, Alasdair [1 ,3 ]
机构
[1] Univ KwaZulu Natal UKZN, KwaZulu Natal Res Inst TB & HIV K RITH, ZA-4001 Durban, South Africa
[2] Univ Copenhagen, Dept Immunol & Microbiol, DK-2200 Copenhagen, Denmark
[3] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA
[4] MIT, Dept Chem, Cambridge, MA 02139 USA
[5] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[6] Broad Inst MIT & Harvard, Cambridge, MA 02139 USA
[7] Karolinska Inst, Ctr Infect Med, S-17176 Stockholm, Sweden
[8] UKZN, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa
[9] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England
[10] ASTAR, Singapore Immunol Network SIgN, Singapore 138632, Singapore
[11] Inkosi Albert Luthuli Hosp, Dept Surg, ZA-4058 Durban, South Africa
[12] Stanger Hosp, ENT Dept, ZA-4450 Durban, South Africa
[13] UKZN, Dept Infect Dis, ZA-4001 Durban, South Africa
[14] CAPRISA, ZA-4001 Durban, South Africa
[15] Univ Cape Town, Div Med Virol, ZA-7925 Cape Town, South Africa
[16] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa
[17] Columbia Univ, Dept Epidemiol, New York, NY 10027 USA
[18] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02138 USA
[19] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
[20] Max Planck Inst Infect Biol, D-10117 Berlin, Germany
基金
美国国家科学基金会;
关键词
T-CELLS; INFLAMMATION; ACTIVATION; TISSUES; OCCURS;
D O I
10.1016/j.immuni.2016.01.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:391 / 405
页数:15
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