{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:28:59Z","timestamp":1789658939453,"version":"4.0.1"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32502990"],"award-info":[{"award-number":["32502990"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32473024"],"award-info":[{"award-number":["32473024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32502990"],"award-info":[{"award-number":["32502990"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32473024"],"award-info":[{"award-number":["32473024"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515110054"],"award-info":[{"award-number":["2024A1515110054"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Project of Department of Education of Guangdong Province","award":["2025KCXTD045"],"award-info":[{"award-number":["2025KCXTD045"]}],"id":[{"id":"https:\/\/ror.org\/01s5gyw91","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2025KCXTD045"],"award-info":[{"award-number":["2025KCXTD045"]}],"id":[{"id":"https:\/\/ror.org\/01s5gyw91","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Project of Graduate Education Innovation Plan of Guangdong Province","award":["2025KCJS_093"],"award-info":[{"award-number":["2025KCJS_093"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Streptococcus equi subsp. zooepidemicus (SEZ) causes severe infections, but the role of the negative regulator interleukin-1 receptor-associated kinase M (IRAK-M) in SEZ-induced inflammation is unclear. In this study, male C57BL\/6 mice received a single intraperitoneal injection of SEZ at 2 \u00d7 107 CFU and were examined 24 h post-injection. SEZ infection triggered overt jejunal hemorrhage and upregulation of IL-1\u03b2, IL-6, and TNF-\u03b1 mRNA, confirming local inflammation, with a concurrent marked reduction in both mRNA and protein levels of IRAK M in the jejunum, hinting at its possible role. We next used IRAK-M knockout (IRAK-M\u2212\/\u2212) mice and found that, compared with the WT+SEZ group, the knockout group displayed more severe jejunal hemorrhage, histopathological scores, and neutrophil infiltration, along with a higher bacterial burden and further elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokine expression. Mechanistically, IRAK-M deficiency in the jejunum further increased the mRNA expression of MyD88, TRIF, TRAF6, IKK\u03b1+\u03b2, NF-\u03baBp50, and NF-\u03baBp65 and decreased I\u03baB\u03b1 mRNA compared with the WT+SEZ group. These findings were paralleled at the protein level, as demonstrated by Western blotting for MyD88, TRAF6, and IKK\u03b1+\u03b2, and by immunofluorescence in peritoneal macrophages. Importantly, IRAK-M deficiency drove a shift toward the M1 macrophage phenotype in both jejunal tissues and peritoneal macrophages, characterized by upregulation of CD16, CD32, CD80, CD86, iNOS, and MHC II, and downregulation of the M2-associated markers Arg1 and CD206. These findings reveal that SEZ infection causes jejunal inflammation and that IRAK-M knockout worsens this condition, pointing to a role for IRAK-M in regulating inflammatory readouts in this model.<\/jats:p>","DOI":"10.3390\/microorganisms14092068","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:50:27Z","timestamp":1789566627000},"page":"2068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum"],"prefix":"10.3390","volume":"14","author":[{"given":"Yuxin","family":"Che","sequence":"first","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Yi","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xinyi","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Junxi","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yixin","family":"Xiu","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Taoyu","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xiaoshu","family":"Zhan","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Jiedan","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Yunfei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Yaqiong","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Ziteng","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, Foshan 528225, 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