Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection

被引：42

作者：

Lal, Kerri G. ^{[1
,2
,3
]}

Kim, Dohoon ^{[1
,2
]}

Costanzo, Margaret C. ^{[1
,2
]}

Creegan, Matthew ^{[1
,2
]}

Leeansyah, Edwin ^{[3
,4
]}

Dias, Joana ^{[3
]}

Paquin-Proulx, Dominic ^{[1
,2
]}

Eller, Leigh Anne ^{[1
,2
]}

Schuetz, Alexandra ^{[1
,2
,5
]}

Phuang-ngern, Yuwadee ^{[5
]}

Krebs, Shelly J. ^{[1
,2
]}

Slike, Bonnie M. ^{[1
,2
]}

Kibuuka, Hannah ^{[6
]}

Maganga, Lucas ^{[7
]}

Nitayaphan, Sorachai ^{[8
]}

Kosgei, Josphat ^{[9
]}

Sacdalan, Carlo ^{[10
]}

Ananworanich, Jintanat ^{[1
,2
,10
]}

Bolton, Diane L. ^{[1
,2
]}

Michael, Nelson L. ^{[1
]}

Shacklett, Barbara L. ^{[11
]}

Robb, Merlin L. ^{[1
,2
]}

Eller, Michael A. ^{[1
,2
]}

Sandberg, Johan K. ^{[3
]}

机构：

[1] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA

[2] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA

[3] Karolinska Inst, Ctr Infect Med, Dept Med, Stockholm, Sweden

[4] Duke Natl Univ Singapore, Program Emerging Infect Dis, Med Sch, Singapore, Singapore

[5] Armed Forces Res Inst Med Sci, Dept Retrovirol, Bangkok, Thailand

[6] Makerere Univ Walter Reed Project, Kampala, Uganda

[7] Mbeya Med Res Ctr, Natl Inst Med Res, Mbeya, Tanzania

[8] Armed Forces Res Inst Med Sci, Royal Thai Army Component, Bangkok, Thailand

[9] US Army Med Res Directorate Africa Kenya, Kenya Med Res Inst, Kericho, Kenya

[10] SEARCH, Thai Red Cross AIDS Res Ctr, Bangkok, Thailand

[11] Univ Calif Davis, Dept Med Microbiol & Immunol, Sch Med, Davis, CA 95616 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

瑞典研究理事会; 美国国家卫生研究院;

关键词：

INVARIANT T-CELLS; ACTIVATION; SUBSET; EXHAUSTION; PROGRAM; GENES;

D O I：

10.1038/s41467-019-13975-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality. Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.

引用

页数：13

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