{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:48:22Z","timestamp":1782982102792,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,29]]},"group-title":"Immunology","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Antibiotics (ABXs) represent the current standard of care for treating\n                  <jats:italic>Clostridioides difficile<\/jats:italic>\n                  infection (CDI). Paradoxically, ABX-induced dysbiosis is the primary risk factor for CDI, as disruption of the colonic microbial ecosystem creates an opportunity for\n                  <jats:italic>C. difficile<\/jats:italic>\n                  colonization. Given that ABXs can also alter immune responses, we investigated whether ABXs prime the colonic immune milieu for CDI susceptibility. Here, we implicate ABXs in driving CDI severity through the emergence of pathogenic CCR5-reliant immune populations in the mouse colon. High-throughput immune cell profiling revealed that ABXs shift the colonic immune compartment toward a CCR5-associated type I immunity signature, marked by an expansion of CCR5\n                  <jats:sup>+<\/jats:sup>\n                  ILC1s and CCR5\n                  <jats:sup>+<\/jats:sup>\n                  Th1 cells. A partial genetic deletion of CCR5 reversed CDI severity, alleviating colonic inflammation and improving survival. Pharmacological inhibition of the CCL3\/4\/5-CCR5 circuit also recapitulated these favorable disease outcomes, which we attribute to reduced colonic CCR5\n                  <jats:sup>+<\/jats:sup>\n                  ILC1, CCR5\n                  <jats:sup>+<\/jats:sup>\n                  Th1, and CCR5\n                  <jats:sup>+<\/jats:sup>\n                  CD8 T cell populations during CDI. Together, our findings extend beyond dysbiosis as the canonical CDI risk factor and establish ABX-induced immune imbalance as an underappreciated determinant of CDI susceptibility.\n                <\/jats:p>","DOI":"10.64898\/2026.06.24.734321","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:20:12Z","timestamp":1782796812000},"source":"Crossref","is-referenced-by-count":0,"title":["Antibiotics promote susceptibility to\n                  <i>C. difficile<\/i>\n                  infection through a CCR5-dependent immune response"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2466-7198","authenticated-orcid":false,"given":"Md. Jashim","family":"Uddin","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5677-0977","authenticated-orcid":false,"given":"Nick R.","family":"Natale","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"},{"name":"Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, Virginia, USA"},{"name":"Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farha","family":"Naz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Tian","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9355-4202","authenticated-orcid":false,"given":"Rachel","family":"McMillan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0106-6020","authenticated-orcid":false,"given":"Duncan J.","family":"Hart","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4075-5939","authenticated-orcid":false,"given":"Shelby L.","family":"Schenck","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-1218","authenticated-orcid":false,"suffix":"Jr.","given":"William A.","family":"Petri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"},{"name":"Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, Virginia, USA"},{"name":"Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA"},{"name":"Department of Pathology, School of Medicine, University of Virginia, Charlottesville, 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