TY - JOUR
T1 - Intracellular immune sensing promotes inflammation via gasdermin D–driven release of a lectin alarmin
AU - Russo, Ashley J.
AU - Vasudevan, Swathy O.
AU - Méndez-Huergo, Santiago P.
AU - Kumari, Puja
AU - Menoret, Antoine
AU - Duduskar, Shivalee
AU - Wang, Chengliang
AU - Pérez Sáez, Juan M.
AU - Fettis, Margaret M.
AU - Li, Chuan
AU - Liu, Renjie
AU - Wanchoo, Arun
AU - Chandiran, Karthik
AU - Ruan, Jianbin
AU - Vanaja, Sivapriya Kailasan
AU - Bauer, Michael
AU - Sponholz, Christoph
AU - Hudalla, Gregory A.
AU - Vella, Anthony T.
AU - Zhou, Beiyan
AU - Deshmukh, Sachin D.
AU - Rabinovich, Gabriel A.
AU - Rathinam, Vijay A.
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85098618450
U2 - 10.1038/s41590-020-00844-7
DO - 10.1038/s41590-020-00844-7
M3 - Article
C2 - 33398185
SN - 1529-2908
VL - 22
SP - 154
EP - 165
JO - Nature Immunology
JF - Nature Immunology
IS - 2
ER -