Intracellular immune sensing promotes inflammation via gasdermin D-driven release of a lectin alarmin.

Autor: Russo AJ; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Vasudevan SO; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Méndez-Huergo SP; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Kumari P; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Menoret A; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA.; Institute for Systems Genomics, University of Connecticut Health, Farmington, CT, USA., Duduskar S; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany., Wang C; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Pérez Sáez JM; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Fettis MM; Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.; AbbVie Bioresearch Center, Worcester, MA, USA., Li C; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Liu R; Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA., Wanchoo A; Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA., Chandiran K; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Ruan J; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Vanaja SK; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Bauer M; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.; Department for Anesthesiology & Intensive Care Medicine, Jena University Hospital, Jena, Germany., Sponholz C; Department for Anesthesiology & Intensive Care Medicine, Jena University Hospital, Jena, Germany., Hudalla GA; Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA., Vella AT; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Zhou B; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA., Deshmukh SD; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany., Rabinovich GA; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.; Faculty of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina., Rathinam VA; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA. Rathinam@uchc.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2021 Feb; Vol. 22 (2), pp. 154-165. Date of Electronic Publication: 2021 Jan 04.
DOI: 10.1038/s41590-020-00844-7
Abstrakt: Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a β-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.
Databáze: MEDLINE