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

Preciado-Llanes, Lorena, Aulicino, Anna, Canals, Rocío, Moynihan, Patrick J., Zhu, Xiaojun, Jambo, Ndaru, Nyirenda, Tonney S., Kadwala, Innocent, Sousa Gerós, Ana, Owen, Siân V., Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Kumwenda, Benjamin, Veerapen, Natacha, Besra, Gurdyal S., Gordon, Melita A., Hinton, Jay C. D., Napolitani, Giorgio, Salio, Mariolina and Simmons, Alison (2020) 'Evasion of MAIT cell recognition by the African Salmonella Typhimurium ST313 pathovar that causes invasive disease'. Proceedings of the National Academy of Sciences, Vol 117, Issue 34, pp. 20717-20728.

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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.

Item Type:	Article
Subjects:	QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350 Anti-bacterial agents (General or not elsewhere classified) QV Pharmacology > QV 38 Drug action. QW Microbiology and Immunology > Bacteria > QW 131 Gram-negative bacteria. QW Microbiology and Immunology > Bacteria > QW 138 Enterobacteriaceae WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General) WI Digestive System > WI 407 Diarrhea
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.2007472117
Depositing User:	Rachael O'Donoghue
Date Deposited:	06 Oct 2020 12:54
Last Modified:	06 Oct 2020 12:54
URI:	https://archive.lstmed.ac.uk/id/eprint/15754

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