Evasion of MAIT cell recognition by the AfricanSalmonellaTyphimurium ST313 pathovar that causes invasive disease

Preciado-Llanes L., Aulicino A., Canals R., Moynihan PJ., Zhu X., Jambo N., Nyirenda TS., Kadwala I., Sousa Gerós A., Owen SV., Jambo KC., Kumwenda B., Veerapen N., Besra GS., Gordon MA., Hinton JCD., Napolitani G., Salio M., Simmons A.

<jats:p>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<jats:italic>Salmonella enterica</jats:italic>strains activate MAIT cells. However,<jats:italic>S.</jats:italic>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<jats:italic>ribB</jats:italic>. 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<jats:italic>ribB</jats:italic>overexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis of<jats:italic>S.</jats:italic>Typhimurium ST313 lineage 2.</jats:p>

DOI

10.1073/pnas.2007472117

Type

Journal article

Journal

Proceedings of the National Academy of Sciences

Publisher

Proceedings of the National Academy of Sciences

Publication Date

25/08/2020

Volume

117

Pages

20717 - 20728

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