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The Inc CpoS is a critical suppressor of host cellular immune surveillance, but the underlying mechanism remained elusive. By complementing a\n                    <jats:italic>cpoS<\/jats:italic>\n                    mutant with various natural orthologs and variants of CpoS, we linked distinct molecular interactions of CpoS to distinct functions. Unexpectedly, we found CpoS to be essential for the formation of inclusion membrane microdomains that control the spatial organization of multiple Incs involved in signaling and modulation of the host cellular cytoskeleton. While the function of CpoS in microdomains was uncoupled from its role in the suppression of host cellular defenses, we found the ability of CpoS to interact with Rab GTPases to be required not only for the manipulation of membrane trafficking, such as to mediate transport of ceramide-derived lipids (sphingolipids) to the inclusion, but also for the inhibition of Stimulator of interferon genes (STING)-dependent type I interferon responses. Indeed, depletion of Rab35 phenocopied the exacerbated interferon responses observed during infection with CpoS-deficient mutants. Overall, our findings highlight the role of Inc\u2013Inc interactions in shaping the inclusion microenvironment and the modulation of membrane trafficking as a pathogenic immune evasion strategy.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                      is a prevalent bacterial pathogen that causes blinding ocular scarring and urogenital infections that can lead to infertility and pregnancy complications. Because\n                      <jats:italic>Chlamydia<\/jats:italic>\n                      can only grow within its host cell, boosting the intrinsic defenses of human cells may represent a novel strategy to fight pathogen replication and survival. Hence, CpoS, a\n                      <jats:italic>Chlamydia<\/jats:italic>\n                      protein known to block host cellular defenses, or processes regulated by CpoS, could provide new opportunities for therapeutic intervention. By revealing CpoS as a multifunctional virulence factor and by linking its ability to block host cellular immune signaling to the modulation of membrane trafficking, the present work may provide a foundation for such rationale targeting and advances our understanding of how intracellular bacteria can shape and protect their growth niche.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03190-22","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T09:00:36Z","timestamp":1690966836000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["The\n                    <i>Chlamydia<\/i>\n                    effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35"],"prefix":"10.1128","author":[{"given":"Karsten","family":"Meier","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University , Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana H.","family":"Jachmann","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University , Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde","family":"T\u00fcrk\u00f6z","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University , Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Rizwan","family":"Babu Sait","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University , Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University , Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University , Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Kepp","sequence":"additional","affiliation":[{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy , Villejuif, France"},{"name":"Centre de Recherche des Cordeliers, Equipe labellis\u00e9e par la Ligue contre le cancer, Universit\u00e9 de Paris, Sorbonne Universit\u00e9, Inserm U1138, Institut Universitaire de France , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael H.","family":"Valdivia","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University School of Medicine , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Kroemer","sequence":"additional","affiliation":[{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy , Villejuif, France"},{"name":"Centre de Recherche des Cordeliers, Equipe 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