Evasion of MAIT cell recognition by the African Salmonella Typhimurium ST313 pathovar that causes invasive disease

Research output: Contribution to journalArticlepeer-review

Authors

  • Lorena Preciado-Llanes
  • Anna Aulicino
  • Rocío Canals
  • Xiaojun Zhu
  • Ndaru Jambo
  • Tonney S Nyirenda
  • Innocent Kadwala
  • Ana Sousa Gerós
  • Siân V Owen
  • Kondwani C Jambo
  • Benjamin Kumwenda
  • Melita A Gordon
  • Jay C D Hinton
  • Giorgio Napolitani
  • Mariolina Salio
  • Alison Simmons

Colleges, School and Institutes

External organisations

  • Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; Department of Oncology, University of Oxford, Oxford, UK.
  • University of Liverpool, Liverpool, UK; The Royal Liverpool University Hospital, Liverpool, UK.
  • School of Biosciences (former MSc student)
  • Univ Birmingham Edgbaston
  • Department of Surgery, College of Medicine, University of Malawi, Blantyre, Malawi; School of Medicine, Flinders University, Adelaide, SA, Australia.
  • Harvard Medical School

Abstract

Mucosal-associated invariant T (MAIT) cells are innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defense. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with selective absence of MAIT cells have not been identified. We report that typhoidal and nontyphoidal Salmonella enterica strains activate MAIT cells. However, S. Typhimurium sequence type 313 (ST313) lineage 2 strains, which are responsible for the burden of multidrug-resistant nontyphoidal invasive disease in Africa, escape MAIT cell recognition through overexpression of ribB This bacterial gene encodes the 4-dihydroxy-2-butanone-4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. The MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose that ribB overexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis of S. Typhimurium ST313 lineage 2.

Bibliographic note

Copyright © 2020 the Author(s). Published by PNAS.

Details

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Publication statusE-pub ahead of print - 11 Aug 2020