Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.,Nature Communications

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Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-14 , DOI: 10.1038/s41467-019-13975-9
Kerri G Lal _{1,

2,

3} , Dohoon Kim _{1,

2} , Margaret C Costanzo _{1,

2} , Matthew Creegan _{1,

2} , Edwin Leeansyah _{3,

4} , Joana Dias ₃ , Dominic Paquin-Proulx _{1,

2} , Leigh Anne Eller _{1,

2} , Alexandra Schuetz _{1,

2,

5} , Yuwadee Phuang-Ngern ₅ , Shelly J Krebs _{1,

2} , Bonnie M Slike _{1,

2} , Hannah Kibuuka ₆ , Lucas Maganga ₇ , Sorachai Nitayaphan ₈ , Josphat Kosgei ₉ , Carlo Sacdalan ₁₀ , Jintanat Ananworanich _{1,

2,

10} , Diane L Bolton _{1,

2} , Nelson L Michael ₁ , Barbara L Shacklett ₁₁ , Merlin L Robb _{1,

2} , Michael A Eller _{1,

2} , Johan K Sandberg ₃

Affiliation

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore.
Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Makerere University Walter Reed Project, Kampala, Uganda.
National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.
Royal Thai Army Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Kenya Medical Research Institute/U.S. Army Medical Research Directorate-Africa/Kenya, Kericho, Kenya.
SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.

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.

中文翻译：

在急性 HIV-1 感染期间具有逐渐增强的先天性的动态 MAIT 细胞反应。

慢性 HIV-1 感染中的黏膜相关不变 T (MAIT) 细胞丢失是对抗菌免疫防御的重大损害。在这里，我们利用 RV217 队列与成对的纵向感染前和感染后样本研究 MAIT 细胞在急性 HIV-1 感染期间的反应。MAIT 细胞在血液和黏膜中被激活并在 HIV-1 病毒血症高峰期扩张，其方式与新出现的微生物易位有关。随后是一个功能升高的阶段，因为病毒复制被控制在设定点水平，然后在慢性感染开始时它们的功能下降。有趣的是，增强的先天样途径和特征在感染期间在 MAIT 细胞中逐渐发展，与 TCR 库的改变平行。

更新日期：2020-01-14

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