African Salmonella Typhimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB



Preciado-Llanes, Lorena, Aulicino, Anna, Canals, Rocío, Moynihan, Patrick, Zhu, Xiaojun, Jambo, Ndaru, Nyirenda, Tonney, Kadwala, Innocent, Owen, Siân V, Veerapen, Natacha
et al (show 6 more authors) (2020) African Salmonella Typhimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB. Proceedings of the National Academy of Sciences of USA.

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Abstract

<jats:title>SUMMARY</jats:title><jats:p>Mucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defence. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with a selective absence of MAIT cells have not been identified. We report that typhoidal and non-typhoidal <jats:italic>S. enterica</jats:italic> strains generally activate MAIT cells. However, African invasive disease-associated multidrug-resistant <jats:italic>S.</jats:italic> Typhimurium sequence type 313 lineage 2 strains escape MAIT cell recognition through overexpression of <jats:italic>ribB</jats:italic>, a bacterial gene that encodes the 4-dihydroxy-2-butanone 4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. This 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 sequence type 313 lineage 2 <jats:italic>in vivo</jats:italic>.</jats:p>

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 07 Jul 2020 07:47
Last Modified: 14 May 2021 11:17
DOI: 10.1101/762955
Open Access URL: https://doi.org/10.1073/pnas.2007472117
URI: https://livrepository.liverpool.ac.uk/id/eprint/3093041