Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli.

PLoS Biology
Caroline BoulouisEdwin Leeansyah

Abstract

Mucosa-associated invariant T (MAIT) cells are abundant antimicrobial T cells in humans and recognize antigens derived from the microbial riboflavin biosynthetic pathway presented by the MHC-Ib-related protein (MR1). However, the mechanisms responsible for MAIT cell antimicrobial activity are not fully understood, and the efficacy of these mechanisms against antibiotic resistant bacteria has not been explored. Here, we show that MAIT cells mediate MR1-restricted antimicrobial activity against Escherichia coli clinical strains in a manner dependent on the activity of cytolytic proteins but independent of production of pro-inflammatory cytokines or induction of apoptosis in infected cells. The combined action of the pore-forming antimicrobial protein granulysin and the serine protease granzyme B released in response to T cell receptor (TCR)-mediated recognition of MR1-presented antigen is essential to mediate control against both cell-associated and free-living, extracellular forms of E. coli. Furthermore, MAIT cell-mediated bacterial control extends to multidrug-resistant E. coli primary clinical isolates additionally resistant to carbapenems, a class of last resort antibiotics. Notably, high levels of granulysin and granzyme B ...Continue Reading

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Citations

Sep 30, 2020·Science Immunology·Tiphaine ParrotJohan K Sandberg
Aug 8, 2020·Mucosal Immunology·Jonna BisterNiklas K Björkström
Oct 21, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yu LiuXiufang Weng
Dec 24, 2020·Trends in Microbiology·Edwin LeeansyahJohan K Sandberg
Dec 29, 2020·The Journal of Infectious Diseases·Ornella SortinoIrini Sereti
Aug 21, 2021·Accounts of Chemical Research·Jeffrey Y W MakDavid P Fairlie
Aug 17, 2021·The Journal of Infectious Diseases·Ornella SortinoIrini Sereti
Aug 18, 2021·The Journal of Allergy and Clinical Immunology·Min-Seok RhaEui-Cheol Shin

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Methods Mentioned

BETA
flow cytometry
fluorescence-activated cell sorting
transgenic
dissection
density gradient separation
density gradient centrifugation
biopsies
FACS
fluorescence microscopy

Software Mentioned

GraphPad
Prism
SPICE
FACSDiva
FlowJo
TreeStar

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