{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:21:39Z","timestamp":1785410499495,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,11]]},"group-title":"Microbiology","reference-count":102,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH-NIAID","award":["R01AI128530"],"award-info":[{"award-number":["R01AI128530"]}]},{"name":"NIH-NIAID","award":["R01AI139102A1"],"award-info":[{"award-number":["R01AI139102A1"]}]},{"name":"NIH-NIAID","award":["R21AI163596A1"],"award-info":[{"award-number":["R21AI163596A1"]}]},{"award":["PATH Award"],"award-info":[{"award-number":["PATH Award"]}],"id":[{"id":"https:\/\/ror.org\/01d35cw23","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Salmonella enterica<\/jats:italic>\n                  comprises over 2500 serovars that are responsible for over 90 million annual infections and 100,000 deaths worldwide. Despite this diversity, our understanding of innate immune responses to\n                  <jats:italic>Salmonella<\/jats:italic>\n                  is based on extensive study of a few serovars, primarily Typhimurium, including strains that cannot replicate within primary murine macrophages. Non-replicating\n                  <jats:italic>Salmonella<\/jats:italic>\n                  trigger caspase-1 and \u221211-dependent pyroptosis. Whether the innate immune system distinguishes between replicating and non-replicating intracellular\n                  <jats:italic>Salmonella<\/jats:italic>\n                  is poorly defined. Here we demonstrate that replicating\n                  <jats:italic>Salmonella enterica<\/jats:italic>\n                  induce a distinct pathway of TNF- and caspase-8-driven apoptosis via host TLR4 and\n                  <jats:italic>Salmonella<\/jats:italic>\n                  Pathogenicity Island-2 activity. This pathway is independent of gasdermin D and involves the apoptotic pore protein Pannexin-1. Combined loss of Pannexin-1 and gasdermin D resulted in defective control of systemic\n                  <jats:italic>Salmonella<\/jats:italic>\n                  , indicating that these pathways function together to promote anti-\n                  <jats:italic>Salmonella<\/jats:italic>\n                  host defense. Altogether, our findings uncover a previously unappreciated pathway by which macrophages sense intracellular replicating bacteria.\n                <\/jats:p>","DOI":"10.1101\/2025.09.10.675376","type":"posted-content","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T03:55:11Z","timestamp":1757649311000},"source":"Crossref","is-referenced-by-count":1,"title":["Innate detection of\n                  <i>Salmonella<\/i>\n                  replication triggers caspase-8-dependent apoptosis via TLR-driven TNF signaling and NLRC4-mediated sensing of the SPI-2 Type III secretion system"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2508-9043","authenticated-orcid":false,"given":"Beatrice I.","family":"Herrmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Zamba-Campero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyna","family":"Garcia-Sillas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winslow W.","family":"Yost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2458-6678","authenticated-orcid":false,"given":"Lance W.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5609-6959","authenticated-orcid":false,"given":"Justin L.","family":"Roncaioili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-540X","authenticated-orcid":false,"given":"Shelley C.","family":"Rankin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-2969","authenticated-orcid":false,"given":"Dieter M.","family":"Schifferli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9049-1410","authenticated-orcid":false,"given":"Kodi","family":"Ravichandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7970-872X","authenticated-orcid":false,"given":"Igor E.","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025101504551151000_2025.09.10.675376v3.1","first-page":"e05500","article-title":"The European Union summary report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2017","volume":"16","author":"European Food Safety, A., European Centre for Disease, P. & Control","year":"2018","journal-title":"EFSA J"},{"key":"2025101504551151000_2025.09.10.675376v3.2","unstructured":"Prevention, C.f.D.C.a. 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