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CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease

Author

Listed:
  • Yi Duan

    (University of California San Diego
    VA San Diego Healthcare System)

  • Huikuan Chu

    (University of California San Diego
    Huazhong University of Science and Technology)

  • Katharina Brandl

    (University of California San Diego)

  • Lu Jiang

    (University of California San Diego
    VA San Diego Healthcare System)

  • Suling Zeng

    (University of California San Diego
    VA San Diego Healthcare System)

  • Nairika Meshgin

    (University of California San Diego)

  • Eleni Papachristoforou

    (Edinburgh BioQuarter)

  • Josepmaria Argemi

    (Pittsburgh Liver Research Center
    University of Navarra)

  • Beatriz G. Mendes

    (University of California San Diego)

  • Yanhan Wang

    (University of California San Diego
    VA San Diego Healthcare System)

  • Hua Su

    (University of California San Diego)

  • Weizhong Sun

    (University of California San Diego)

  • Cristina Llorente

    (University of California San Diego)

  • Tim Hendrikx

    (University of California San Diego)

  • Xiao Liu

    (University of California San Diego
    University of California San Diego)

  • Mojgan Hosseini

    (University of California San Diego)

  • Tatiana Kisseleva

    (University of California San Diego)

  • David A. Brenner

    (University of California San Diego)

  • Ramon Bataller

    (Pittsburgh Liver Research Center)

  • Prakash Ramachandran

    (Edinburgh BioQuarter)

  • Michael Karin

    (University of California San Diego)

  • Wenxian Fu

    (University of California San Diego
    Genentech)

  • Bernd Schnabl

    (University of California San Diego
    VA San Diego Healthcare System)

Abstract

Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg–Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease.

Suggested Citation

  • Yi Duan & Huikuan Chu & Katharina Brandl & Lu Jiang & Suling Zeng & Nairika Meshgin & Eleni Papachristoforou & Josepmaria Argemi & Beatriz G. Mendes & Yanhan Wang & Hua Su & Weizhong Sun & Cristina Ll, 2021. "CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27385-3
    DOI: 10.1038/s41467-021-27385-3
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