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Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in <jats:italic>T. pallidum<\/jats:italic> infection remains unclear. Tp92 is the only <jats:italic>T. pallidum<\/jats:italic> helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram\u2010negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short\u2010lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase\u20103 via the ERK MAPK, PI3K\/Akt, and NF\u2010\u03baB signaling pathways, consequently suppressing caspase\u20103 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti\u2010apoptotic protein Mcl\u20101, stimulating IL\u20108 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying <jats:italic>T. pallidum<\/jats:italic> infection and suggest potential therapeutic targets for syphilis treatment.<\/jats:p>","DOI":"10.1111\/mmi.15164","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T06:20:49Z","timestamp":1695018049000},"page":"684-701","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The outer membrane protein Tp92 of <i>Treponema pallidum<\/i> delays human neutrophil apoptosis via the <scp>ERK<\/scp>, <scp>PI3K<\/scp>\/<scp>Akt<\/scp>, and <scp>NF\u2010\u03baB<\/scp> pathways"],"prefix":"10.1111","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4897-6817","authenticated-orcid":false,"given":"Weiwei","family":"Li","sequence":"first","affiliation":[{"name":"Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical 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