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

Kerri G Lal,Dohoon Kim,Edwin Leeansyah,Bonnie M Slike,Josphat Kosgei,Matthew Creegan,Shelly J Krebs,Diane L Bolton,Nelson L Michael,Sorachai Nitayaphan,Barbara L Shacklett,Merlin L Robb,Carlo Sacdalan,Yuwadee Phuang-Ngern,Michael A Eller,Joana Dias,Hannah Kibuuka,Margaret C Costanzo,Leigh Anne Eller,Dominic Paquin‐Proulx ,Lucas Maganga,Alexandra Schuetz,Jintanat Ananworanich,Johan K Sandberg

doi:10.1038/s41467-019-13975-9

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.

Highlights

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses
We investigate the response of MAIT cells during the first critical days and weeks of acute HIV-1 infection utilizing longitudinal pre-infection and post-infection samples from the RV217 Early Capture HIV Cohort Study (ECHO)[34]
MAIT cell dynamics were examined during the earliest stages of acute HIV-1 infection in 29 individuals from the RV217 ECHO study[34], for which cryopreserved autologous longitudinal samples were available from pre-infection time points, followed by samples taken within days from the first detection of HIV-1 RNA and further out into chronic infection (Supplementary Table 1)

Summary

Introduction

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. 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. MAIT cells with the capacity to respond to antigen-presenting cell (APC)-derived cytokines[9], recently shown to be important for enhancement of TCR-mediated MAIT cell activation[19,20], and for triggering of MR1-independent MAIT cell responses[21,22,23] Such MR1-independent responses, including production of IFNγ, may be important for the involvement of MAIT cells in viral diseases[24,25,26,27,28]. MAIT cells are poised to respond to infection from a variety of pathogens and can possibly influence disease outcome

Methods

Results

Conclusion