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Interferon\u2010gamma (IFN\u2010\u03b3) binding to macrophages impacts the expression of approximately 2000 genes, activating them to enhance intracellular bactericidal activity. While various immune evasion strategies of\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    have been extensively studied, the specific mechanisms by which it suppresses IFN\u2010\u03b3\u2010mediated macrophage activation remain insufficiently characterized. In this study, we elucidated the molecular mechanism by which\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    suppresses interferon signaling in macrophages, with a particular focus on\n                    <jats:italic>STAT1<\/jats:italic>\n                    transcript abundance, because\n                    <jats:italic>STAT1<\/jats:italic>\n                    encodes a central transcription factor in the IFN\u2010\u03b3 pathway. RNA\u2010seq analysis revealed that\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    infection reduced the mRNA abundance of approximately 41% of genes upregulated following IFN\u2010\u03b3 stimulation, including\n                    <jats:italic>STAT1<\/jats:italic>\n                    transcripts and other interferon\u2010related genes. Further experiments showed that direct contact between the bacterium and host cells is necessary for this inhibition. This process involves the Type IX Secretion System (T9SS) and gingipains. Notably, strains lacking all gingipains (Kgp, RgpA, and RgpB) failed to suppress\n                    <jats:italic>STAT1<\/jats:italic>\n                    transcript abundance and instead allowed nuclear translocation of phosphorylated STAT1. These gingipain\u2010deficient strains also exhibited reduced invasive ability, correlating with their diminished capacity to suppress interferon signaling and macrophage activation. In conclusion, our findings demonstrate that\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    inhibits interferon signaling in macrophages through intracellular infiltration, with T9SS and gingipains playing essential roles in this immunosuppressive mechanism. These results provide valuable insights into the immune evasion strategies of\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    and suggest potential therapeutic targets for combating periodontopathic diseases.\n                  <\/jats:p>","DOI":"10.1002\/mbo3.70290","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:11:56Z","timestamp":1776053516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Porphyromonas gingivalis<\/i>\n                    Suppresses Interferon\u2010Gamma Signaling in Macrophages Through a Contact\u2010Dependent, Gingipain\u2010Mediated Mechanism"],"prefix":"10.1002","volume":"15","author":[{"given":"Shotaro","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Restorative Dentistry and Endodontology, Graduate School of Dentistry The University of Osaka Suita Osaka 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikako","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Endodontology, Graduate School of Dentistry The University of Osaka Suita Osaka 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