TY - JOUR
T1 - Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections
AU - Edmans, Matthew D.
AU - Connelley, Timothy K.
AU - Jayaraman, Siddharth
AU - Vrettou, Christina
AU - Vordermeier, Martin
AU - Mak, Jeffrey Y.W.
AU - Liu, Ligong
AU - Fairlie, David P.
AU - Maze, Emmanuel Atangana
AU - Chrun, Tiphany
AU - Klenerman, Paul
AU - Eckle, Sidonia B.G.
AU - Tchilian, Elma
AU - Benedictus, Lindert
N1 - Funding Information:
We are grateful to the staff of the Dryden farm of the Roslin Institute and the animal staff at the APHA for their invaluable help with the animal experiments. We also thank the Pirbright flow cytometry facility (National capability science services) for their support with flow cytometry and the Roslin Institute Veterinary Immunological Toolbox facility for support with monoclonal antibody production. Funding. This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC, Grant numbers BB N004647/1, BBS/E/I/00007031, BBS/E/I/00007038 and BBS/E/I/00007039) and the bovine tuberculosis research budget held and administered centrally by the UK Department for Environment, Food and Rural affairs on behalf of England, Scotland and Wales (Project Code SE3299). Work performed at the University of Oxford was supported by the Wellcome Trust (WT109965MA), NIHR Senior Fellowship (PK). Work at the Roslin Institute is supported by Strategic Program Grants from the BBSRC. SE was supported by an Australian Research Council DECRA fellowship (DE170100407) and an Australian National Health and Medical Research Council Project grant (APP1157388). DF is supported by a Senior Principal Research Fellowship (1117017) from the Australian Research Council (CE140100011) and National Health and Medical Research Council of Australia (NHMRC).
Publisher Copyright:
© Copyright © 2021 Edmans, Connelley, Jayaraman, Vrettou, Vordermeier, Mak, Liu, Fairlie, Maze, Chrun, Klenerman, Eckle, Tchilian and Benedictus.
PY - 2021/3/11
Y1 - 2021/3/11
N2 - Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilize a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such as Mycobacterium spp., Salmonella spp. and Escherichia coli. To date, MAIT cells have been studied in humans, non-human primates and mice. However, they have only been putatively identified in cattle by PCR based methods; no phenotypic or functional analyses have been performed. Here, we identified a MAIT cell population in cattle utilizing MR1 tetramers and high-throughput TCR sequencing. Phenotypic analysis of cattle MAIT cells revealed features highly analogous to those of MAIT cells in humans and mice, including expression of an orthologous TRAV1-TRAJ33 TCR α chain, an effector memory phenotype irrespective of tissue localization, and expression of the transcription factors PLZF and EOMES. We determined the frequency of MAIT cells in peripheral blood and multiple tissues, finding that cattle MAIT cells are enriched in mucosal tissues as well as in the mesenteric lymph node. Cattle MAIT cells were responsive to stimulation by 5-OP-RU and riboflavin biosynthesis competent bacteria in vitro. Furthermore, MAIT cells in milk increased in frequency in cows with mastitis. Following challenge with virulent Mycobacterium bovis, a causative agent of bovine tuberculosis and a zoonosis, peripheral blood MAIT cells expressed higher levels of perforin. Thus, MAIT cells are implicated in the immune response to two major bacterial infections in cattle. These data suggest that MAIT cells are functionally highly conserved and that cattle are an excellent large animal model to study the role of MAIT cells in important zoonotic infections.
AB - Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilize a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such as Mycobacterium spp., Salmonella spp. and Escherichia coli. To date, MAIT cells have been studied in humans, non-human primates and mice. However, they have only been putatively identified in cattle by PCR based methods; no phenotypic or functional analyses have been performed. Here, we identified a MAIT cell population in cattle utilizing MR1 tetramers and high-throughput TCR sequencing. Phenotypic analysis of cattle MAIT cells revealed features highly analogous to those of MAIT cells in humans and mice, including expression of an orthologous TRAV1-TRAJ33 TCR α chain, an effector memory phenotype irrespective of tissue localization, and expression of the transcription factors PLZF and EOMES. We determined the frequency of MAIT cells in peripheral blood and multiple tissues, finding that cattle MAIT cells are enriched in mucosal tissues as well as in the mesenteric lymph node. Cattle MAIT cells were responsive to stimulation by 5-OP-RU and riboflavin biosynthesis competent bacteria in vitro. Furthermore, MAIT cells in milk increased in frequency in cows with mastitis. Following challenge with virulent Mycobacterium bovis, a causative agent of bovine tuberculosis and a zoonosis, peripheral blood MAIT cells expressed higher levels of perforin. Thus, MAIT cells are implicated in the immune response to two major bacterial infections in cattle. These data suggest that MAIT cells are functionally highly conserved and that cattle are an excellent large animal model to study the role of MAIT cells in important zoonotic infections.
KW - bovine tuberculosis
KW - cattle
KW - mastitis
KW - MR1 tetramer
KW - mucosal-associated invariant T cells
KW - T cell receptor
KW - unconventional T cell
UR - http://www.scopus.com/inward/record.url?scp=85103050849&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.627173
DO - 10.3389/fimmu.2021.627173
M3 - Article
C2 - 33777010
AN - SCOPUS:85103050849
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 627173
ER -
