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The abnormal enhancement of microglial phagocytosis can cause damage to the nervous system. However, the contribution of abnormally enhanced microglial phagocytosis to the pathogenesis of <jats:italic>Treponema pallidum<\/jats:italic> subsp. <jats:italic>pallidum<\/jats:italic> (<jats:italic>T. pallidum<\/jats:italic>) infection remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In this study, we sought to determine the role of recombinant <jats:italic>T. pallidum<\/jats:italic> Tp47 in promoting microglia phagocytosis and its associated mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Microglial HMC3 cells were used to investigate the effect of the Tp47 on phagocytosis and the roles of autophagy and endoplasmic reticulum stress in Tp47\u2010induced phagocytosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HMC3 cells exhibited obvious phagocytosis when stimulated with Tp47. The levels of P62 degradation, Beclin1 expression and the LC3II\/LC3I ratio were significantly elevated, and the fusion of autophagosomes and lysosomes was promoted in Tp47\u2010stimulated HMC3 cells. Treatment with the autophagy inhibitors 3\u2010MA and Baf A1 inhibited Tp47\u2010induced phagocytosis. Meanwhile, the endoplasmic reticulum stress markers PERK, IRE1\u03b1, GRP78, ATF4 and XBP1s were upregulated in Tp47\u2010stimulated HMC3 cells. In addition, we found that TUDCA could inhibit Tp47\u2010induced expression of IRE1\u03b1 but not PERK or ATF4. 4\u2010PBA inhibited TP47\u2010induced PERK and ATF4 protein expression but did not inhibit IRE1\u03b1 expression. Attenuation of endoplasmic reticulum stress by administration of TUDCA and 4\u2010PBA abrogated Tp47\u2010mediated autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggested that Tp47 activated autophagy through two key pathways associated with endoplasmic reticulum stress, PERK\/ATF4 and IRE1\/XBP1, to promote phagocytosis in HMC3 cells. These findings provided a basis for the understanding of the pathophysiology of neurological disorders that occur during the course of syphilis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.18295","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T16:38:14Z","timestamp":1654533494000},"page":"2224-2234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Tp47 promoted the phagocytosis of <scp>HMC3<\/scp> cells though autophagy induced by endoplamic reticlum stress"],"prefix":"10.1111","volume":"36","author":[{"given":"W.","family":"Li","sequence":"first","affiliation":[{"name":"Center of Clinical Laboratory Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q.\u2010L.","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q.\u2010Y.","family":"Xu","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X.\u2010T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4303-6252","authenticated-orcid":false,"given":"T.\u2010C.","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen China"},{"name":"Institute of Infectious Disease, School of 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