학술논문
Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.
Document Type
article
Author
Lal, Kerri G; Kim, Dohoon; Costanzo, Margaret C; Creegan, Matthew; Leeansyah, Edwin; Dias, Joana; Paquin-Proulx, Dominic; Eller, Leigh Anne; Schuetz, Alexandra; Phuang-Ngern, Yuwadee; Krebs, Shelly J; Slike, Bonnie M; Kibuuka, Hannah; Maganga, Lucas; Nitayaphan, Sorachai; Kosgei, Josphat; Sacdalan, Carlo; Ananworanich, Jintanat; Bolton, Diane L; Michael, Nelson L; Shacklett, Barbara L; Robb, Merlin L; Eller, Michael A; Sandberg, Johan K
Source
Nature communications. 11(1)
Subject
Language
Abstract
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.