TY - JOUR
T1 - Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection
AU - Lal, Kerri G.
AU - Kim, Dohoon
AU - Costanzo, Margaret C.
AU - Creegan, Matthew
AU - Leeansyah, Edwin
AU - Dias, Joana
AU - Paquin-Proulx, Dominic
AU - Eller, Leigh Anne
AU - Schuetz, Alexandra
AU - Phuang-ngern, Yuwadee
AU - Krebs, Shelly J.
AU - Slike, Bonnie M.
AU - Kibuuka, Hannah
AU - Maganga, Lucas
AU - Nitayaphan, Sorachai
AU - Kosgei, Josphat
AU - Sacdalan, Carlo
AU - Ananworanich, Jintanat
AU - Bolton, Diane L.
AU - Michael, Nelson L.
AU - Shacklett, Barbara L.
AU - Robb, Merlin L.
AU - Eller, Michael A.
AU - Sandberg, Johan K.
N1 - Funding Information:
The MR1 tetramer technology was developed jointly by Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie, and the material was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne. RNA-Seq samples were processed in the Molecular Analysis Core Facility at SUNY Upstate Medical University (Syracuse, NY). The authors would like to thank the RV217 Study Team, as well as the RV304/SEARCH 013 and RV254/SEARCH 010 Study Groups for conduct of the clinical research and collection of samples. The authors also thank Rasmi Thomas for critical review of this paper. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). This research was funded, in part, by the U.S. National Institute of Allergy and Infectious Disease. This research was further supported by grants to J.K.S. from the Swedish Research Council (2016-03052) and the Swedish Cancer Society (CAN 2017/777). B.L.S., J.K.S., and M.A.E. were jointly supported by US National Institutes of Health grant (R01DK108350). The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077844981&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13975-9
DO - 10.1038/s41467-019-13975-9
M3 - Article
C2 - 31937782
AN - SCOPUS:85077844981
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 272
ER -