{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:10:04Z","timestamp":1791216604401,"version":"4.1.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971147, 82271387"],"award-info":[{"award-number":["81971147, 82271387"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key projects of the Natural Science Foundation of Fujian Province","award":["No. 2022J02055"],"award-info":[{"award-number":["No. 2022J02055"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J01073"],"award-info":[{"award-number":["2021J01073"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Fund of the National Natural Science Foundation of China","award":["82001292"],"award-info":[{"award-number":["82001292"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    (\n                    <jats:italic>Tp<\/jats:italic>\n                    ) has a well-known ability to evade the immune system and can cause neurosyphilis by invading the central nervous system (CNS). Microglia are resident macrophages of the CNS that are essential for host defense against pathogens, this study aims to investigate the interaction between\n                    <jats:italic>Tp<\/jats:italic>\n                    and microglia and the potential mechanism. Here, we found that\n                    <jats:italic>Tp<\/jats:italic>\n                    can exert significant toxic effects on microglia in vivo in Tg (mpeg1: EGFP) transgenic zebrafish embryos. Single-cell RNA sequencing results showed that\n                    <jats:italic>Tp<\/jats:italic>\n                    downregulated autophagy-related genes in human HMC3 microglial cells, which is negatively associated with apoptotic gene expression. Biochemical and cell biology assays further established that\n                    <jats:italic>Tp<\/jats:italic>\n                    inhibits microglial autophagy by interfering with the autophagosome-lysosome fusion process. Transcription factor EB (TFEB) is a master regulator of lysosome biogenesis,\n                    <jats:italic>Tp<\/jats:italic>\n                    activates the mechanistic target of rapamycin complex 1 (mTORC1) signaling to inhibit the nuclear translocation of TFEB, leading to decreased lysosomal biogenesis and accumulated autophagosome. Importantly, the inhibition of autophagosome formation reversed\n                    <jats:italic>Tp<\/jats:italic>\n                    -induced apoptosis and promoted microglial clearance of\n                    <jats:italic>Tp<\/jats:italic>\n                    . Taken together, these findings show that\n                    <jats:italic>Tp<\/jats:italic>\n                    blocks autophagic flux by inhibiting TFEB-mediated lysosomal biosynthesis in human microglia. Autophagosome accumulation was demonstrated to be a key mechanism underlying the effects of\n                    <jats:italic>Tp<\/jats:italic>\n                    in promoting apoptosis and preventing itself from clearing by human microglia. This study offers novel perspectives on the potential mechanism of immune evasion employed by\n                    <jats:italic>Tp<\/jats:italic>\n                    within CNS. The results not only establish the pivotal role of autophagy dysregulation in the detrimental effects of\n                    <jats:italic>Tp<\/jats:italic>\n                    on microglial cells but also bear considerable implications for the development of therapeutic strategies against\n                    <jats:italic>Tp<\/jats:italic>\n                    , specifically involving mTORC1 inhibitors and autophagosome formation inhibitors, in the context of neurosyphilis patients.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011594","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T13:24:50Z","timestamp":1692797090000},"page":"e1011594","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Treponema pallidum promoted microglia apoptosis and prevented itself from clearing by human microglia via blocking autophagic flux"],"prefix":"10.1371","volume":"19","author":[{"given":"Yun-Ting","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Xuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Tong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Yi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Li","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4968-4266","authenticated-orcid":true,"given":"Li-Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"issue":"29","key":"ppat.1011594.ref001","doi-asserted-by":"crossref","first-page":"E844","DOI":"10.1503\/cmaj.200189","article-title":"Neurosyphilis","volume":"192","author":"S Peermohamed","year":"2020","journal-title":"Cmaj"},{"issue":"5","key":"ppat.1011594.ref002","first-page":"315","article-title":"Current concepts of the morphology and biology of Treponema pallidum based on electron microscopy","volume":"47","author":"NM Ovcinnikov","year":"1971","journal-title":"Br J Vener Dis"},{"issue":"2","key":"ppat.1011594.ref003","first-page":"87","article-title":"Serial ultrathin sectioning demonstrating the intracellularity of T. 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