title: Unconventional Human T Cells Accumulate at the Site of Infection in Response to Microbial Ligands and Induce Local Tissue Remodeling.
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 Vγ9/Vδ2(+) γδ 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-γ and TNF-α 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 Vγ9/Vδ2 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.
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Liuzzi
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;
authors.forename: Ann
authors.identifier: 0000-0001-8083-2760
authors.initials: A
authors.lastname: Kift-Morgan
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom; Wales Kidney Research Unit, Heath Park Campus, Cardiff CF14 4XN, United Kingdom;
authors.forename: Melisa
authors.initials: M
authors.lastname: Lopez-Anton
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;
authors.forename: Ida M
authors.identifier: 0000-0002-3139-7384
authors.initials: IM
authors.lastname: Friberg
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;
authors.forename: Amy C
authors.identifier: 0000-0001-8374-2218
authors.initials: AC
authors.lastname: Brook
authors.affiliation: Wales Kidney Research Unit, Heath Park Campus, Cardiff CF14 4XN, United Kingdom; Directorate of Nephrology and Transplantation, Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff CF14 4XW, United Kingdom;
authors.forename: Gareth W
authors.identifier: 0000-0003-4496-6539
authors.initials: GW
authors.lastname: Roberts
authors.affiliation: Wales Kidney Research Unit, Heath Park Campus, Cardiff CF14 4XN, United Kingdom; Directorate of Nephrology and Transplantation, Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff CF14 4XW, United Kingdom;
authors.forename: Kieron L
authors.initials: KL
authors.lastname: Donovan
authors.affiliation: Wales Kidney Research Unit, Heath Park Campus, Cardiff CF14 4XN, United Kingdom;
authors.forename: Chantal S
authors.identifier: 0000-0003-4370-3163
authors.initials: CS
authors.lastname: Colmont
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;
authors.forename: Mark A
authors.initials: MA
authors.lastname: Toleman
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom; Wales Kidney Research Unit, Heath Park Campus, Cardiff CF14 4XN, United Kingdom;
authors.forename: Timothy
authors.identifier: 0000-0001-6050-0435
authors.initials: T
authors.lastname: Bowen
authors.affiliation: Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia; Centre for Kidney Disease Research, Translational Research Institute, Brisbane, Queensland 4102, Australia; Australia and New Zealand Dialysis and Transplant Registry, Adelaide, South Australia 5001, Australia;
authors.forename: David W
authors.identifier: 0000-0001-5491-3460
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Centre for Medical Education, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom; and Systems Immunity Research Institute, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Nicholas
authors.identifier: 0000-0003-2925-4779
authors.initials: N
authors.lastname: Topley
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom; Systems Immunity Research Institute, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Bernhard
authors.identifier: 0000-0002-4354-4572
authors.initials: B
authors.lastname: Moser
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom; Wales Kidney Research Unit, Heath Park Campus, Cardiff CF14 4XN, United Kingdom; Directorate of Nephrology and Transplantation, Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff CF14 4XW, United Kingdom; Systems Immunity Research Institute, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Donald J
authors.identifier: 0000-0003-0102-9342
authors.initials: DJ
authors.lastname: Fraser
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom; Systems Immunity Research Institute, Cardiff University, Cardiff CF14 4XN, United Kingdom eberlm@cf.ac.uk.
authors.forename: Matthias
authors.identifier: 0000-0002-9390-5348
authors.initials: M
authors.lastname: Eberl
mesh_terms: D001424:Bacterial Infections / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D020556:Neutrophil Infiltration; D010538:Peritonitis / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008024:Ligands; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma