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

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 14, 2020
Source ID
10.1038/s41467-019-13975-9

Entities

People

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

Organizations

  • National Institute of Diabetes and Digestive and Kidney Diseases
  • Swedish Cancer Society
  • Swedish Research Council
  • United States Department of Defense

Tags

Fields of Study

  • Medicine

Readers

  • Molecular and Cellular Biology
  • Software Engineering.
  • Virology (or Medical Virology).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech