Unconventional human T cells accumulate at the site of infection in response to microbial ligands and induce local tissue remodeling

Liuzzi, Anna Rita, Kift-Morgan, Ann, Lopez-Anton, Melisa, Friberg, Ida M., Zhang, Jingjing ORCID: https://orcid.org/0000-0002-8970-7568, Brook, Amy C., Roberts, Gareth W., Donovan, Kieron L., Colmont, Chantal S., Toleman, Mark A., Bowen, Timothy ORCID: https://orcid.org/0000-0001-6050-0435, Johnson, David W., Topley, Nicholas, Moser, Bernhard ORCID: https://orcid.org/0000-0002-4354-4572, Fraser, Donald J. ORCID: https://orcid.org/0000-0003-0102-9342 and Eberl, Matthias ORCID: https://orcid.org/0000-0002-9390-5348 2016. Unconventional human T cells accumulate at the site of infection in response to microbial ligands and induce local tissue remodeling. Journal of Immunology 197 (6) , pp. 2195-2207. 10.4049/jimmunol.1600990

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Abstract

The antimicrobial responsiveness and function of unconventional human T cells are poorly understood, with only limited access to relevant specimens from sites of infection. Peritonitis is a common and serious complication in individuals with end-stage kidney disease receiving peritoneal dialysis. By analyzing local and systemic immune responses in peritoneal dialysis patients presenting with acute bacterial peritonitis and monitoring individuals before and during defined infectious episodes, our data show that Vg9/ Vd2+ gd T cells and mucosal-associated invariant T cells accumulate at the site of infection with organisms producing (E)-4- hydroxy-3-methyl-but-2-enyl pyrophosphate and vitamin B2, respectively. Such unconventional human T cells are major producers of IFN-g and TNF-a in response to these ligands that are shared by many microbial pathogens and affect the cells lining the peritoneal cavity by triggering local inflammation and inducing tissue remodeling with consequences for peritoneal membrane integrity. Our data uncover a crucial role for Vg9/Vd2 T cells and mucosal-associated invariant T cells in bacterial infection and suggest that they represent a useful predictive marker for important clinical outcomes, which may inform future stratification and patient management. These findings are likely to be applicable to other acute infections where local activation of unconventional T cells contributes to the antimicrobial inflammatory response.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	The American Association of Immunologists, Inc
ISSN:	0022-1767
Date of First Compliant Deposit:	22 August 2016
Date of Acceptance:	8 July 2016
Last Modified:	09 May 2023 19:35
URI:	https://orca.cardiff.ac.uk/id/eprint/93873

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