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Despite the efficacy of antibiotic treatment in controlling syphilis, the pathogenic mechanisms of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    , particularly its interactions with the host immune system, are not well understood. This study aimed to investigate the potential immunomodulatory role of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    enolase (Eno) in promoting macrophage apoptosis through the P2X7R and reactive oxygen species (ROS)\/NF\u2010\u03baB pathways, offering new insights into the pathogen's immune evasion strategies. Bioinformatics analysis identified\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    Eno as a hydrophilic cytoplasmic protein that plays a crucial role in glycolysis. In\u00a0vitro experiments demonstrated that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    Eno can be successfully expressed and purified in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                    <\/jats:styled-content>\n                    , resulting in significant induction of macrophage apoptosis. Mechanistic studies revealed that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    Eno activates caspase family members, decreases mitochondrial membrane potential, and triggers the apoptotic program in macrophages. Additionally, we found that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    Eno stimulates the production of ROS, subsequently activating the NF\u2010\u03baB signaling pathway and promoting the transcription of apoptosis\u2010related genes. This study further highlights the role of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    Eno in modulating host immune responses by inducing the secretion of interleukin\u20108, interleukin\u20106, and interleukin\u20101\u03b2, which are involved in macrophage chemotaxis and activation. Collectively, these findings suggest that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    may exploit the host inflammatory response to enhance its dissemination and evade immune clearance. The multifaceted functions of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>T.\u2009pallidum<\/jats:italic>\n                    <\/jats:styled-content>\n                    Eno in cell metabolism and immune regulation provide new insights into the pathogenesis of syphilis and offer potential targets for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500358r","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T10:44:28Z","timestamp":1751453068000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Regulatory Mechanisms of\n                    <i>Treponema pallidum<\/i>\n                    Enolase on Macrophages: From Enzymatic Activity to Signal Transduction"],"prefix":"10.1096","volume":"39","author":[{"given":"Peiyuan","family":"Sun","sequence":"first","affiliation":[{"name":"Hunan Province 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