Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens
Summary: Host cell cytosol is monitored by inflammasomes. Cytosolic invasion of pathogens involves breaching endolysosomal membranes, which is sensed by galectins triggering endolysosomal damage response. Whether and how endomembrane damage surveillance impacts inflammasome sensing of pathogens is u...
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725007739 |
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| author | Sonia Shivcharan Doulathunnisa Ahamed Younis Skylar S. Wright Chengliang Wang Bharat Behl Patience Shumba Kristina N. Delgado Arshmeet K. Chawla Neal M. Alto Noorjahan Panjwani Sivapriya Kailasan Vanaja Jianbin Ruan Zhichao Fan Vijay A. Rathinam |
| author_facet | Sonia Shivcharan Doulathunnisa Ahamed Younis Skylar S. Wright Chengliang Wang Bharat Behl Patience Shumba Kristina N. Delgado Arshmeet K. Chawla Neal M. Alto Noorjahan Panjwani Sivapriya Kailasan Vanaja Jianbin Ruan Zhichao Fan Vijay A. Rathinam |
| author_sort | Sonia Shivcharan |
| collection | DOAJ |
| description | Summary: Host cell cytosol is monitored by inflammasomes. Cytosolic invasion of pathogens involves breaching endolysosomal membranes, which is sensed by galectins triggering endolysosomal damage response. Whether and how endomembrane damage surveillance impacts inflammasome sensing of pathogens is unknown. Here, we show that endosomal damage sensing by galectin-8 licenses rapid noncanonical inflammasome sensing of intracellular bacteria; caspase-4 sensing of cytosol-invading bacteria, the consequent gasdermin D (GSDMD)-mediated pyroptosis, and interleukin (IL)-18 activation are greatly reduced in galectin-8-deficient human epithelial cells. Interestingly, galectin-8 promotes caspase-4 activation independently of the autophagic receptor NDP52 and bacterial restriction. Instead, we demonstrate that galectin-8 exists in a complex with caspase-4 in naive cells and recruits caspase-4 to bacteria upon endolysosomal rupture, enabling lipopolysaccharide (LPS) sensing. Collectively, this study reveals galectin-8 as a hub integrating endomembrane damage sensing and inflammasome sensing. Thus, tethering the pathogen sensor caspase-4 to the endomembrane damage sensor galectin-8 poises the host to rapidly detect bacteria that breach the endolysosomal network. |
| format | Article |
| id | doaj-art-be8d12cc4e304075b92e30a7b3c29d19 |
| institution | Matheson Library |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-be8d12cc4e304075b92e30a7b3c29d192025-07-17T04:44:17ZengElsevierCell Reports2211-12472025-08-01448116002Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogensSonia Shivcharan0Doulathunnisa Ahamed Younis1Skylar S. Wright2Chengliang Wang3Bharat Behl4Patience Shumba5Kristina N. Delgado6Arshmeet K. Chawla7Neal M. Alto8Noorjahan Panjwani9Sivapriya Kailasan Vanaja10Jianbin Ruan11Zhichao Fan12Vijay A. Rathinam13Department of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Medicine, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USANew England Eye Center, Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USADepartment of Immunology, UConn Health School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA; Corresponding authorSummary: Host cell cytosol is monitored by inflammasomes. Cytosolic invasion of pathogens involves breaching endolysosomal membranes, which is sensed by galectins triggering endolysosomal damage response. Whether and how endomembrane damage surveillance impacts inflammasome sensing of pathogens is unknown. Here, we show that endosomal damage sensing by galectin-8 licenses rapid noncanonical inflammasome sensing of intracellular bacteria; caspase-4 sensing of cytosol-invading bacteria, the consequent gasdermin D (GSDMD)-mediated pyroptosis, and interleukin (IL)-18 activation are greatly reduced in galectin-8-deficient human epithelial cells. Interestingly, galectin-8 promotes caspase-4 activation independently of the autophagic receptor NDP52 and bacterial restriction. Instead, we demonstrate that galectin-8 exists in a complex with caspase-4 in naive cells and recruits caspase-4 to bacteria upon endolysosomal rupture, enabling lipopolysaccharide (LPS) sensing. Collectively, this study reveals galectin-8 as a hub integrating endomembrane damage sensing and inflammasome sensing. Thus, tethering the pathogen sensor caspase-4 to the endomembrane damage sensor galectin-8 poises the host to rapidly detect bacteria that breach the endolysosomal network.http://www.sciencedirect.com/science/article/pii/S2211124725007739CP: Immunology |
| spellingShingle | Sonia Shivcharan Doulathunnisa Ahamed Younis Skylar S. Wright Chengliang Wang Bharat Behl Patience Shumba Kristina N. Delgado Arshmeet K. Chawla Neal M. Alto Noorjahan Panjwani Sivapriya Kailasan Vanaja Jianbin Ruan Zhichao Fan Vijay A. Rathinam Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens Cell Reports CP: Immunology |
| title | Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens |
| title_full | Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens |
| title_fullStr | Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens |
| title_full_unstemmed | Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens |
| title_short | Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens |
| title_sort | endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725007739 |
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