Kupffer cell-like syncytia replenish resident macrophage function in the fibrotic liver

• 成果类型: Article
• 署名作者: Peiseler, Moritz; David, Bruna Araujo; Zindel, Joel; Surewaard, Bas G. J.; Lee, Woo-Yong; Heymann, Felix; Nusse, Ysbrand; Castanheira, Fernanda V. S.; Shim, Raymond; Guillot, Adrien; Bruneau, Alix; Atif, Jawairia; Perciani, Catia; Ohland, Christina; Mukherjee, Priyanka Ganguli; Niehrs, Annika; Thuenauer, Roland; Altfeld, Marcus; Amrein, Mathias; Liu, Zhaoyuan; Gordon, Paul M. K.; McCoy, Kathy; Deniset, Justin; MacParland, Sonya; Ginhoux, Florent; Tacke, Frank; Kubes, Paul
• 署名单位: University of Calgary; University of Calgary; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Humboldt University of Berlin; Free University of Berlin; Charite Universitatsmedizin Berlin; Berlin Institute of Health; University of Bern; University of Toronto; University Health Network Toronto; Toronto General Hospital; University of Calgary; Chinese Academy of Sciences; Shanghai Jiao Tong University; University of Calgary; University of Calgary; University of Calgary; University of Calgary; Libin Cardiovascular Institute Of Alberta; Agency for Science Technology & Research (A*STAR); A*STAR - Singapore Immunology Network (SIgN); Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Gustave Roussy; Universite Paris Saclay
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11270
• DOI: 10.1126/science.abq5202
• 发表日期: 2023-09-08
• 页码: 1066-+
• 关键词: disease; homeostasis; receptor; capture; subset; SYSTEM; crig

摘要

Kupffer cells (KCs) are localized in liver sinusoids but extend pseudopods to parenchymal cells to maintain their identity and serve as the body's central bacterial filter. Liver cirrhosis drastically alters vascular architecture, but how KCs adapt is unclear. We used a mouse model of liver fibrosis and human tissue to examine immune adaptation. Fibrosis forced KCs to lose contact with parenchymal cells, down-regulating KC identity, which rendered them incapable of clearing bacteria. Commensals stimulated the recruitment of monocytes through CD44 to a spatially distinct vascular compartment. There, recruited monocytes formed large aggregates of multinucleated cells (syncytia) that expressed phenotypical KC markers and displayed enhanced bacterial capture ability. Syncytia formed via CD36 and were observed in human cirrhosis as a possible antimicrobial defense that evolved with fibrosis.