Journal Article

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

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

2020

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/1 / 13/21 / 13/31 / 38 / 38/39 / 38/62 / 38/91 / 631/250 / 631/250/2152 / 631/250/2499 / 631/250/255 / 631/250/262 / Antiinfectives and antibacterials / Biomarkers - blood / Biomarkers - metabolism / C-Reactive Protein - metabolism / Chronic infection / Cohort Studies / HIV / HIV Infections - immunology / HIV-1 - physiology / Human immunodeficiency virus / Humanities and Social Sciences / Humans / Immunity, Innate - genetics / Infections / Interferon Regulatory Factors - genetics / Interferon Regulatory Factors - metabolism / Invariants / Lipopolysaccharide Receptors - metabolism / Lymphocyte Activation / Microorganisms / Mucosa / Mucosal-Associated Invariant T Cells - immunology / Mucosal-Associated Invariant T Cells - metabolism / Mucosal-Associated Invariant T Cells - microbiology / multidisciplinary / Receptors, Antigen, T-Cell - genetics / Receptors, Antigen, T-Cell - metabolism / Science / Science (multidisciplinary) / T cell receptors / Transcriptome / Translocation / Viremia / Viremia - immunology