PLX207219

GSE79833: CRIG identifies a novel population of highly phagocytic peritoneal macrophages associated with disease severity in patients with cirrhosis and ascites

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesising 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 sub-populations. The proportion of CRIgHi macrophages differed between patients, and in the same patient over time, and a high proportion of CRIgHi macrophages was associated with reduced disease severity (Model for End Stage Liver Disease (MELD)) score. As compared to CRIgLow macrophages, CRIgHi macrophages 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 between CRIgHi cells, human macrophages and mouse F4/80Hi resident peritoneal macrophages, and between CRIgLow macrophages, human monocytes and mouse F4/80Low monocyte-derived peritoneal macrophages. These data suggest CRIgHi and CRIgLow macrophages 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 between patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients. SOURCE: Katharine Irvine (k.irvine@imb.uq.edu.au, m.sweet@imb.uq.edu.au) - Institute for Molecular Bioscience