title: CRIg-expressing peritoneal macrophages are associated with disease severity in patients with cirrhosis and ascites.
abstract: Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesizing that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage subpopulations. The proportion of CRIghimacrophages differed between patients and in the same patient over time, and a high proportion of CRIghimacrophages was associated with reduced disease severity (model for end-stage liver disease) score. As compared with CRIglomacrophages, CRIghimacrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities among CRIghicells, human macrophages, and mouse F4/80hiresident peritoneal macrophages and among CRIglomacrophages, human monocytes, and mouse F4/80lomonocyte-derived peritoneal macrophages. These data suggest that CRIghiand CRIglomacrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable among patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients.
authors.affiliation: School of Medicine.
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Irvine
authors.affiliation: School of Medicine.
authors.forename: Xuan
authors.initials: X
authors.lastname: Banh
authors.affiliation: School of Medicine.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Gadd
authors.affiliation: School of Medicine.
authors.forename: Kyle K
authors.initials: KK
authors.lastname: Wojcik
authors.affiliation: Institute for Molecular Bioscience (IMB), and.|IMB Centre for Inflammation and Disease Research, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Juliana K
authors.initials: JK
authors.lastname: Ariffin
authors.affiliation: School of Medicine.
authors.forename: Sara
authors.initials: S
authors.lastname: Jose
authors.affiliation: Institute for Molecular Bioscience (IMB), and.
authors.forename: Samuel
authors.initials: S
authors.lastname: Lukowski
authors.affiliation: Institute for Molecular Bioscience (IMB), and.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Baillie
authors.affiliation: Institute for Molecular Bioscience (IMB), and.|IMB Centre for Inflammation and Disease Research, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sweet
authors.affiliation: School of Medicine.|Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Powell
mesh_terms: D000368:Aged; D000818:Animals; D001201:Ascites / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D017737:Macrophages, Peritoneal / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011951:Receptors, Complement; D017463:Receptors, Complement 3b / Q000378:metabolism*
chemical_list: C509991:CR1 protein, human; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C509992:VSIG4 protein, mouse