{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T15:56:38Z","timestamp":1773762998630,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ9389"],"award-info":[{"award-number":["2024JJ9389"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ9392"],"award-info":[{"award-number":["2024JJ9392"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013090","name":"Science and Technology Innovation Project","doi-asserted-by":"publisher","award":["202330046180"],"award-info":[{"award-number":["202330046180"]}],"id":[{"id":"10.13039\/501100013090","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Basic and Applied Research Program of Hengyang Science and Technology Bureau","award":["202330046377"],"award-info":[{"award-number":["202330046377"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bartonella henselae establishes persistent infections by manipulating host cell survival, but mechanisms beyond the known type IV secretion system (T4SS)-cAMP pathway are poorly understood. Here, we delineate a novel anti-apoptotic axis in human endothelial cells hijacked by B. henselae. We found that infection upregulates the pro-survival factor amphiregulin (AREG). This induction is initiated by the intracellular sensor NOD2, which triggers a PI3K\/AKT\/CREB signaling cascade, culminating in CREB-dependent transcription of AREG. Functional studies confirmed that secreted AREG acts via its receptor, EGFR, to suppress apoptosis, establishing a complete NOD2-AREG-EGFR autocrine loop. Collectively, our findings characterize a sophisticated survival strategy where B. henselae links intracellular innate immune sensing to the activation of an autocrine growth factor loop. The delineation of this novel NOD2-AREG-EGFR axis reveals a parallel mechanism of host cell manipulation, adding a new layer of complexity to our understanding of Bartonella\u2013host interactions.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf566","type":"journal-article","created":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:03:03Z","timestamp":1762606983000},"page":"475-484","source":"Crossref","is-referenced-by-count":0,"title":["<i>Bartonella henselae<\/i>\n                    Subverts Host Cell Apoptosis by Linking Intracellular NOD2 Sensing to an AREG\/EGFR Autocrine Survival Loop"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9356-3256","authenticated-orcid":false,"given":"Jun","family":"He","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, the Second Affiliated Hospital, Hengyang Medical College, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2500-7078","authenticated-orcid":false,"given":"Shutong","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4003-6183","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8125-4151","authenticated-orcid":false,"given":"Yixuan","family":"Xi","sequence":"additional","affiliation":[{"name":"Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2406-3695","authenticated-orcid":false,"given":"Qianrui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9283-1052","authenticated-orcid":false,"given":"Haodang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Urology, the Second Affiliated Hospital, Hengyang Medical College, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7890-6345","authenticated-orcid":false,"given":"Chun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, the Second Affiliated Hospital, Hengyang Medical College, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3821-7121","authenticated-orcid":false,"given":"Lei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, the Second Affiliated Hospital, Hengyang Medical College, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8897-3186","authenticated-orcid":false,"given":"Xiaoxing","family":"You","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, the Second Affiliated Hospital, Hengyang Medical College, University of South China , Hengyang ,","place":["China"]},{"name":"Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China , Hengyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"2026031710034487200_jiaf566-B1","doi-asserted-by":"crossref","first-page":"2322961","DOI":"10.1080\/21505594.2024.2322961","article-title":"Sneaky tactics: ingenious immune evasion mechanisms of 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