Mucosal-Associated Invariant T Cells Redistribute to the Peritoneal Cavity During Spontaneous Bacterial Peritonitis and Contribute to Peritoneal Inflammation

Oluwatomi Ibidapo-Obe; Sven Stengel; Nilay Köse-Vogel; Stefanie Quickert; Philipp A Reuken; Martin Busch; Michael Bauer; Andreas Stallmach; Tony Bruns

doi:10.1016/j.jcmgh.2020.01.003

Mucosal-Associated Invariant T Cells Redistribute to the Peritoneal Cavity During Spontaneous Bacterial Peritonitis and Contribute to Peritoneal Inflammation

Cell Mol Gastroenterol Hepatol. 2020;9(4):661-677. doi: 10.1016/j.jcmgh.2020.01.003. Epub 2020 Jan 15.

Authors

Oluwatomi Ibidapo-Obe¹, Sven Stengel¹, Nilay Köse-Vogel¹, Stefanie Quickert¹, Philipp A Reuken¹, Martin Busch², Michael Bauer³, Andreas Stallmach¹, Tony Bruns⁴

Affiliations

¹ Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany.
² Department of Internal Medicine III, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany.
³ Center for Sepsis Control and Care (CSCC), Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany; Department of Anesthesiology and Intensive Care, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany.
⁴ Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany; Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany. Electronic address: tbruns@ukaachen.de.

Abstract

Background & aims: Mucosal-associated invariant T (MAIT) cells are depleted from blood in patients with advanced liver disease and show features of immune dysfunction. Because circulating MAIT cells differ from organ-resident MAIT cells, we aimed to investigate the frequency, phenotype, and function of peritoneal MAIT cells from patients with cirrhosis and spontaneous bacterial peritonitis (SBP).

Methods: MAIT cells in blood and ascitic fluid from patients with cirrhosis were characterized using flow cytometry. Healthy individuals and noncirrhotic patients undergoing peritoneal dialysis served as controls. MAIT cell migration was studied in transwell assays. Cytokine release in response to infected ascitic fluid and bacterial products was assessed in vitro.

Results: Peritoneal CD3+ CD161hi Vα7.2+ T cells had an inflammatory, tissue retention phenotype, expressing the alpha E integrin, the chemokine receptors CCR5 and CXCR3, and the activation marker CD69 at higher levels than their circulating equivalents. Seventy-seven percent bound to MR1 tetramers loaded with the pyrimidine intermediate 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil. The ratio of peritoneal to blood MAIT cell frequency increased from 1.3 in the absence of SBP to 2.6 at diagnosis and decreased by day 3. MAIT cells migrated toward infected ascitic fluid containing CCL5 and CCL20 and released cytokines in an MR1-restricted fashion. Whereas the depleted circulating MAIT cell pool displayed features of immune exhaustion, peritoneal MAIT cells remained competent producers of inflammatory cytokines in response to bacterial products. Peritoneal MAIT activation correlated with systemic inflammation, suggesting a possible link between peritoneal and systemic immunity.

Conclusions: Peritoneal MAIT cells phenotypically and functionally differ from circulating MAIT cells in decompensated cirrhosis and redistribute to the peritoneum during SBP.

Keywords: Bacterial Infections; Liver Cirrhosis; Mucosal-Associated Invariant T Cells; Spontaneous Bacterial Peritonitis.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Ascitic Fluid / cytology*
Ascitic Fluid / immunology
Bacterial Infections / blood
Bacterial Infections / immunology*
Bacterial Infections / microbiology
Bacterial Infections / pathology
Case-Control Studies
End Stage Liver Disease / blood
End Stage Liver Disease / complications*
End Stage Liver Disease / diagnosis
End Stage Liver Disease / immunology
Female
Follow-Up Studies
Healthy Volunteers
Humans
Liver / pathology
Liver Cirrhosis / blood
Liver Cirrhosis / complications*
Liver Cirrhosis / diagnosis
Liver Cirrhosis / immunology
Male
Middle Aged
Mucosal-Associated Invariant T Cells / immunology*
Peritoneal Cavity / microbiology
Peritoneal Cavity / pathology
Peritonitis / blood
Peritonitis / immunology*
Peritonitis / microbiology
Peritonitis / pathology
Severity of Illness Index