IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum

Che, Yuxin; Xie, Yi; Qiu, Xinyi; Lin, Junxi; Xiu, Yixin; Yu, Taoyu; Zhan, Xiaoshu; Liao, Jiedan; Huang, Yunfei; Ye, Yaqiong; Deng, Ziteng

doi:10.3390/microorganisms14092068

Open AccessArticle

IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum

by

Yuxin Che

^1,2,†,

Yi Xie

^1,2,†,

Xinyi Qiu

^1,2,

Junxi Lin

^1,2,

Yixin Xiu

^1,2,

Taoyu Yu

^1,2,

Xiaoshu Zhan

^1,2,

Jiedan Liao

^1,2,

Yunfei Huang

^1,2,

Yaqiong Ye

^1,2 and

Ziteng Deng

^1,2,*

¹

School of Animal Science and Technology, Foshan University, Foshan 528225, China

²

Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Microorganisms 2026, 14(9), 2068; https://doi.org/10.3390/microorganisms14092068

Submission received: 23 July 2026 / Revised: 8 September 2026 / Accepted: 9 September 2026 / Published: 16 September 2026

(This article belongs to the Section Molecular Microbiology and Immunology)

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Abstract

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 × 10⁷ CFU and were examined 24 h post-injection. SEZ infection triggered overt jejunal hemorrhage and upregulation of IL-1β, IL-6, and TNF-α 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^−/−) 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, IKKα+β, NF-κBp50, and NF-κBp65 and decreased IκBα mRNA compared with the WT+SEZ group. These findings were paralleled at the protein level, as demonstrated by Western blotting for MyD88, TRAF6, and IKKα+β, 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.

Keywords: Streptococcus equi subsp. zooepidemicus; jejunum; interleukin-1 receptor-associated kinase M; NF-κB; macrophage

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MDPI and ACS Style

Che, Y.; Xie, Y.; Qiu, X.; Lin, J.; Xiu, Y.; Yu, T.; Zhan, X.; Liao, J.; Huang, Y.; Ye, Y.; et al. IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum. Microorganisms 2026, 14, 2068. https://doi.org/10.3390/microorganisms14092068

AMA Style

Che Y, Xie Y, Qiu X, Lin J, Xiu Y, Yu T, Zhan X, Liao J, Huang Y, Ye Y, et al. IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum. Microorganisms. 2026; 14(9):2068. https://doi.org/10.3390/microorganisms14092068

Chicago/Turabian Style

Che, Yuxin, Yi Xie, Xinyi Qiu, Junxi Lin, Yixin Xiu, Taoyu Yu, Xiaoshu Zhan, Jiedan Liao, Yunfei Huang, Yaqiong Ye, and et al. 2026. "IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum" Microorganisms 14, no. 9: 2068. https://doi.org/10.3390/microorganisms14092068

APA Style

Che, Y., Xie, Y., Qiu, X., Lin, J., Xiu, Y., Yu, T., Zhan, X., Liao, J., Huang, Y., Ye, Y., & Deng, Z. (2026). IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum. Microorganisms, 14(9), 2068. https://doi.org/10.3390/microorganisms14092068

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IRAK-M Knockout Exacerbates Inflammation in Mice Infected with Streptococcus equi subsp. zooepidemicus: Observation in the Jejunum

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