{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:48:14Z","timestamp":1792000094609,"version":"4.4.0"},"reference-count":80,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    infection is characterized by chronic gastric inflammation driven by persistent activation of innate immune signaling pathways. Outer membrane vesicles (OMVs) released by\n                    <jats:italic>H. pylori<\/jats:italic>\n                    are important mediators of host\u2013pathogen interactions. Although several mechanisms of OMV internalization have been described, how specific OMV\u2010associated bacterial factors engage host innate immune receptors and couple vesicle association to inflammatory signaling remains poorly understood. Here, we investigated the contribution of OMV\u2010associated virulence factors and Toll\u2010like receptor 2 (TLR2) heterodimers to OMV\u2013host cell interactions in gastric epithelial cells. Using engineered AGS and GES\u20101 reporter cells expressing TLR2\/1 or TLR2\/6, together with genetically defined OMVs, we found that\n                    <jats:italic>H. pylori<\/jats:italic>\n                    OMVs preferentially associated with TLR2\u2010expressing cells and induced robust NF\u2010\u03baB activation. Comparative analysis of OMVs from wild\u2010type and isogenic mutant strains identified Neutrophil\u2010Activating Protein A (NapA) as a major determinant of TLR2\u2010dependent OMV association and inflammatory signaling, whereas urease had a more limited contribution. Disruption of NapA or neutralization of TLR2 markedly reduced OMV association with gastric epithelial cells. Purified\n                    <jats:italic>H. pylori<\/jats:italic>\n                    lipopolysaccharide elicited a comparatively weak and TLR2\/6\u2010biased response, indicating that it does not account for the robust TLR2\u2010dependent signaling induced by intact OMVs. Furthermore, OMV\u2010associated NapA exhibited greater pro\u2010inflammatory activity than soluble recombinant NapA, supporting a role for the vesicular context in enhancing TLR2\u2010dependent signaling. Pharmacological inhibition with sulforaphane significantly attenuated OMV\u2010induced TLR2\/NF\u2010\u03baB activation. Collectively, these findings identify a previously unrecognized role for OMV\u2010associated NapA in linking TLR2\u2010dependent vesicle association with gastric epithelial cells to inflammatory signaling and support a model in which vesicular presentation of bacterial factors contributes to innate immune receptor engagement, providing a mechanistic link between the initial OMV\u2013host cell interaction and subsequent inflammatory signalling.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70376","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:50:06Z","timestamp":1790625006000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Helicobacter pylori<\/i>\n                    Outer Membrane Vesicles Engage TLR2 Through NapA to Promote Epithelial Association and Inflammatory Signalling"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5728-0093","authenticated-orcid":false,"given":"Mariaignacia","family":"Rubilar","sequence":"first","affiliation":[{"name":"Laboratorio de Carcinog\u00e9nesis Molecular, Instituto de Investigaci\u00f3n y Doctorados Universidad Central de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosy","family":"Brito","sequence":"additional","affiliation":[{"name":"Laboratorio de Carcinog\u00e9nesis Molecular, Instituto de Investigaci\u00f3n y Doctorados Universidad Central de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegrett","family":"Palavecino","sequence":"additional","affiliation":[{"name":"Laboratorio de Carcinog\u00e9nesis Molecular, Instituto de Investigaci\u00f3n y Doctorados Universidad Central de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3336-1454","authenticated-orcid":false,"given":"Joan","family":"Villena","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinario de Investigaci\u00f3n Biom\u00e9dica e Ingenier\u00eda para la Salud (MEDING), Facultad de Medicina, Campus de la Salud Universidad de Valpara\u00edso  Vi\u00f1a del Mar Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9577-5180","authenticated-orcid":false,"given":"Marco","family":"Mellado","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n de Investigaci\u00f3n Universidad Bernardo O'Higgins  Santiago Chile"},{"name":"Laboratorio de Espectroscop\u00eda y Qu\u00edmica Aplicada Instituto de Investigaci\u00f3n y Doctorados Universidad Central de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda I.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratorio de Carcinog\u00e9nesis Molecular, Instituto de Investigaci\u00f3n y Doctorados Universidad Central de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8833-7382","authenticated-orcid":false,"given":"Manuel","family":"Valenzuela\u2010Valderrama","sequence":"additional","affiliation":[{"name":"Laboratorio de Carcinog\u00e9nesis Molecular, Instituto de Investigaci\u00f3n y Doctorados Universidad Central de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2007.00327.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27177"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-2272"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38605"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01344-13"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i28.3071"},{"key":"e_1_2_9_8_1","first-page":"336","article-title":"Pattern\u2010Recognition Receptors and Gastric Cancer","volume":"5","author":"Castano\u2010Rodriguez N.","year":"2014","journal-title":"Frontiers in 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