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

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

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Article number272
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Lal, K. G., Kim, D., Costanzo, M. C., Creegan, M., Leeansyah, E., Dias, J., Paquin-Proulx, D., Eller, L. A., Schuetz, A., Phuang-ngern, Y., Krebs, S. J., Slike, B. M., Kibuuka, H., Maganga, L., Nitayaphan, S., Kosgei, J., Sacdalan, C., Ananworanich, J., Bolton, D. L., ... Sandberg, J. K. (2020). Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection. Nature communications, 11(1), [272]. https://doi.org/10.1038/s41467-019-13975-9