{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:43:43Z","timestamp":1787510623394,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013033","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anusandhan National Research Foundation (ANRF), Government of India","award":["CRG\/2023\/002323"],"award-info":[{"award-number":["CRG\/2023\/002323"]}]},{"DOI":"10.13039\/501100011652","name":"Indian Institute of Science Education and Research Mohali","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011652","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    cytolysin (VCC) is a potent exotoxin secreted by\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    , the etiological agent of the severe diarrheal disease cholera. VCC is a membrane-damaging pore-forming toxin by nature, and is well known for its ability to cause host cell death. Using wild type\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    and VCC-deleted mutant variant of the bacteria, we show that VCC plays an important role in the inflammatory responses during infection in mice. This observation supports that VCC can function as a pathogen-associated molecular pattern (PAMP). Toll-like receptors (TLRs) are the key initiators of inflammation. Upon ligand recognition, TLR1 and TLR6 generally form heterodimers with TLR2 for triggering pro-inflammatory signals. In the present study, we show that VCC engages novel TLR1\/4 heterodimer assembly, and elicits pro-inflammatory responses in both dendritic cells (DCs) and macrophages. Along with TLR1\/4, VCC-induced pro-inflammatory response in macrophages also involves TLR2. It has been shown earlier that VCC is implicated in the\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    -mediated killing of the immune cells following biofilm formation. Here we show that TLRs play an important role in VCC-mediated killing of DCs and macrophages following\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    infection. Interestingly, we find that TLR1\/4 signalling is specifically crucial for the VCC-induced inflammatory and death responses in DCs, as well as in mice. Additionally, we observe that similar to DCs and macrophages, TLR1\/4-MyD88 play an important role in VCC-mediated inflammatory responses in another crucial immune cell type, neutrophils. Taken together, our study shows novel TLR heterodimer formation, differential recognition of the same ligand by different TLR combination in cell type-dependent manner, and their implications in the context of\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    and VCC-induced immune cell death and mortality.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013033","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T14:16:57Z","timestamp":1743776217000},"page":"e1013033","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Vibrio cholerae cytolysin induces pro-inflammatory and death signals through novel TLR assembly"],"prefix":"10.1371","volume":"21","author":[{"given":"Shraddha","family":"Gandhi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindhoora","family":"Puravankara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anish Kumar","family":"Mondal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakanksha","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi Prakash","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8529-9475","authenticated-orcid":true,"given":"Kausik","family":"Chattopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunika","family":"Mukhopadhaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"issue":"3","key":"ppat.1013033.ref001","doi-asserted-by":"crossref","first-page":"001154","DOI":"10.1099\/mic.0.001154","article-title":"Bacterial pore-forming toxins","volume":"168","author":"FR Ulhuq","year":"2022","journal-title":"Microbiology (Reading)"},{"issue":"1","key":"ppat.1013033.ref002","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1042\/BST20200836","article-title":"Pore-forming toxins in infection and 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