Christian E Niehaus1, Benedikt Strunz2, Anke R M Kraft1,3, Niklas K Björkström2, Markus Cornberg1,3,4,5,6, Martin Cornillet2, Christine S Falk7,3, Ansgar Schnieders1, Benjamin Maasoumy1,3, Svenja Hardtke8, Michael P Manns1,3. 1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. 2. Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. 3. German Center for Infection Research, Partner-Site Hannover-Braunschweig, Hannover, Germany. 4. Centre for Individualised Infection Medicine (CiiM), Hannover, Germany. 5. TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hanover Medical School and the Helmholtz Centre for Infection Research, Braunschweig, Germany. 6. Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany. 7. Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany. 8. German Center for Infection Research, HepNet Study-House German Liver Foundation, Hannover, Germany.
Abstract
BACKGROUND AND AIMS: Patients with advanced liver cirrhosis have an increased susceptibility to infections. As part of the cirrhosis-associated immune dysfunction, mucosal-associated invariant T (MAIT) cells, which have the capacity to respond to bacteria, are severely diminished in circulation and liver tissue. However, MAIT cell presence and function in the peritoneal cavity, a common anatomical site for infections in cirrhosis, remain elusive. In this study, we deliver a comprehensive investigation of the immune compartment present in ascites of patients with decompensated liver cirrhosis, and focus especially on MAIT cells. APPROACH AND RESULTS: To study this, matched peripheral blood and ascites fluid were collected from 35 patients with decompensated cirrhosis, with or without spontaneous bacterial peritonitis (SBP). MAIT cell phenotype and function were analyzed using high-dimensional flow cytometry, and the obtained data were compared with the blood samples of healthy controls (n = 24) and patients with compensated cirrhosis (n = 11). We found circulating MAIT cells to be severely decreased in patients with cirrhosis as compared with controls. In contrast, in ascites fluid, MAIT cells were significantly increased together with CD14+ CD16+ monocytes, innate lymphoid cells, and natural killer cells. This was paralleled by elevated levels of several pro-inflammatory cytokines and chemokines in ascites fluid as compared with plasma. Peritoneal MAIT cells displayed an activated tissue-resident phenotype, and this was corroborated by increased functional responses following stimulation with E. coli or interleukin (lL)-12 + IL-18 as compared with circulating MAIT cells. During SBP, peritoneal MAIT cell frequencies increased most among all major immune cell subsets, suggestive of active homing of MAIT cells to the site of infection. CONCLUSIONS: Despite severely diminished MAIT cell numbers and impaired phenotype in circulation, peritoneal MAIT cells remain abundant, activated, and highly functional in decompensated cirrhosis and are further enriched in SBP. This suggests that peritoneal MAIT cells could be of interest for immune-intervention strategies in patients with decompensated liver cirrhosis and SBP.
BACKGROUND AND AIMS: Patients with advanced liver cirrhosis have an increased susceptibility to infections. As part of the cirrhosis-associated immune dysfunction, mucosal-associated invariant T (MAIT) cells, which have the capacity to respond to bacteria, are severely diminished in circulation and liver tissue. However, MAIT cell presence and function in the peritoneal cavity, a common anatomical site for infections in cirrhosis, remain elusive. In this study, we deliver a comprehensive investigation of the immune compartment present in ascites of patients with decompensated liver cirrhosis, and focus especially on MAIT cells. APPROACH AND RESULTS: To study this, matched peripheral blood and ascites fluid were collected from 35 patients with decompensated cirrhosis, with or without spontaneous bacterial peritonitis (SBP). MAIT cell phenotype and function were analyzed using high-dimensional flow cytometry, and the obtained data were compared with the blood samples of healthy controls (n = 24) and patients with compensated cirrhosis (n = 11). We found circulating MAIT cells to be severely decreased in patients with cirrhosis as compared with controls. In contrast, in ascites fluid, MAIT cells were significantly increased together with CD14+ CD16+ monocytes, innate lymphoid cells, and natural killer cells. This was paralleled by elevated levels of several pro-inflammatory cytokines and chemokines in ascites fluid as compared with plasma. Peritoneal MAIT cells displayed an activated tissue-resident phenotype, and this was corroborated by increased functional responses following stimulation with E. coli or interleukin (lL)-12 + IL-18 as compared with circulating MAIT cells. During SBP, peritoneal MAIT cell frequencies increased most among all major immune cell subsets, suggestive of active homing of MAIT cells to the site of infection. CONCLUSIONS: Despite severely diminished MAIT cell numbers and impaired phenotype in circulation, peritoneal MAIT cells remain abundant, activated, and highly functional in decompensated cirrhosis and are further enriched in SBP. This suggests that peritoneal MAIT cells could be of interest for immune-intervention strategies in patients with decompensated liver cirrhosis and SBP.
Authors: Hema Mehta; Martin Joseph Lett; Paul Klenerman; Magdalena Filipowicz Sinnreich Journal: Semin Immunopathol Date: 2022-05-31 Impact factor: 11.759
Authors: Johanna Reißing; Philipp Lutz; Mick Frissen; Oluwatomi Ibidapo-Obe; Philipp A Reuken; Theresa H Wirtz; Sven Stengel; Stefanie Quickert; Michael Rooney; Karsten Große; Henning W Zimmermann; Christian Trautwein; Andreas Stallmach; Tony Bruns Journal: JHEP Rep Date: 2021-11-03