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DOI: 10.1055/s-0039-3402262
Inflammatory peritoneal MAIT cells accumulate during the early phase of spontaneous bacterial peritonitis
Publikationsverlauf
Publikationsdatum:
03. Januar 2020 (online)
Questions:
Mucosal-associated invariant T (MAIT) cells, which play important roles in anti-bacterial defence, are depleted from blood in advanced liver disease and show features of immune dysfunction. As circulating MAIT cells may differ from organ-resident MAIT cells, we aimed to investigate the frequency, phenotype, and function of peritoneal MAIT cells from patients with cirrhosis in the absence or presence of spontaneous bacterial peritonitis (SBP).
Methods:
MAIT cells were isolated from peripheral blood and ascitic fluid from 100 patients with decompensated cirrhosis using flow cytometry. Whole blood samples from healthy individuals and peritoneal dialysate from non-cirrhotic individuals served as controls. Co-culture experiments were performed to assess the response to PMA/Ionomycin, bacterial culture supernatants, and infected ascitic fluid. The migration of MAIT cells was studied using trans-well migration assays.
Results:
Peritoneal MAIT cells had an inflammatory, tissue retention phenotype expressing the integrins αEβ7 and α4β7, and the chemokine receptors CXCR3, CCR5, and CCR6 at high levels. Whereas MAIT cells were depleted from blood in patients with decompensated cirrhosis, MAIT cells were enriched in the peritoneal cavity at SBP diagnosis. Consistent with their chemokine receptor repertoire, activated MAIT cells preferentially migrated towards infected AF as compared to conventional T cells and were activated in a MR1-restricted fashion. Whereas circulating MAIT cells displayed features of immune exhaustion, peritoneal MAIT cells remained competent producers of interferon gamma and tumor necrosis factor in response to E. coli. In clinical association studies, the state of peritoneal MAIT activation correlated with the severity of systemic inflammation.
Conclusions:
Peritoneal MAIT are functionally competent inflammatory innate immune cells in decompensated cirrhosis, which accumulate during early SBP.