{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:30:38Z","timestamp":1778509838973,"version":"3.51.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    <jats:italic>Vibrio vulnificus<\/jats:italic>\n                    (\n                    <jats:italic>V. vulnificus<\/jats:italic>\n                    ) is a highly virulent zoonotic pathogen causing severe septicemia and tissue necrosis in humans, characterized by a cytokine storm. While bacterial outer membrane vesicles (OMVs) are known to mediate host-pathogen interactions, their specific contribution to\n                    <jats:italic>V. vulnificus<\/jats:italic>\n                    -induced immunopathology remains obscure. In this study, we isolated and characterized\n                    <jats:italic>V. vulnificus<\/jats:italic>\n                    -derived OMVs and investigated their impact on murine macrophages (J774A.1). We demonstrate that these OMVs are actively internalized by macrophages in a time-dependent manner, triggering a robust pro-inflammatory response. Transcriptomic analysis and subsequent validation revealed that internalized OMVs activated the TNF signaling pathway, leading to the phosphorylation of NF-\u03baB and MAPK (p38\/JNK) cascades. Crucially, OMV exposure induced severe mitochondrial dysfunction, evidenced by ultrastructural disruption and a significant reduction in mitochondrial membrane potential. Notably, pharmacological blockade of the TNF receptor with the antagonist R-7050 effectively attenuated this mitochondrial damage. These findings establish a novel pathogenic mechanism wherein\n                    <jats:italic>V. vulnificus<\/jats:italic>\n                    OMVs exploit the host TNF signaling axis to drive mitochondrial injury, providing new insights into the cellular mechanisms of\n                    <jats:italic>V. vulnificus<\/jats:italic>\n                    lethality and suggesting the TNF-mitochondria axis as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2026.1785223","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T13:43:57Z","timestamp":1778507037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vibrio vulnificus outer membrane vesicles induce mitochondrial dysfunction in macrophages via the TNF signaling pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Jun","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luying","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijie","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life 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