Rehydration rescues Il22-/- mice from lethal Citrobacter rodentium infection DOI Creative Commons
Gad Frankel, Vishwas Mishra, Priyanka Paul Biswas

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Interleukin-22 (IL-22) is considered indispensable for host defence against Citrobacter rodentium (CR), with 100% mortality of Il22−/− mice post infection. While IL-22 promotes epithelial barrier integrity and antimicrobial peptide production, the precise mechanism underlying lethality remains unclear. Here, we show that succumb to CR infection due dehydration rather than uncontrolled bacterial burden or inability regenerate intestinal epithelium. Proteomic analysis at 9 days (dpi) revealed significant downregulation ion transporters (Slc26a3, Aqp8, Ca2, Ca4, Slc5a8, Slc15a1) in colonic cells, suggesting an association between deficiency impaired fluid-electrolyte balance. Fluid therapy (FT), initiated 5 dpi lasted 2 weeks, fully rescued mice, restoring survival without affecting burden, immune responses, integrity. Recovered exhibited regeneration protection reinfection, demonstrating IL-22-independent pathways support long-term mucosal recovery. These findings overturn long-standing paradigm from infection, revealing primary cause mortality. Importantly, this study underscores necessity incorporating supportive therapies into preclinical models better reflect physiological conditions enhance translational relevance.

Language: Английский

Rehydration rescues Il22-/- mice from lethal Citrobacter rodentium infection DOI Creative Commons
Gad Frankel, Vishwas Mishra, Priyanka Paul Biswas

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Interleukin-22 (IL-22) is considered indispensable for host defence against Citrobacter rodentium (CR), with 100% mortality of Il22−/− mice post infection. While IL-22 promotes epithelial barrier integrity and antimicrobial peptide production, the precise mechanism underlying lethality remains unclear. Here, we show that succumb to CR infection due dehydration rather than uncontrolled bacterial burden or inability regenerate intestinal epithelium. Proteomic analysis at 9 days (dpi) revealed significant downregulation ion transporters (Slc26a3, Aqp8, Ca2, Ca4, Slc5a8, Slc15a1) in colonic cells, suggesting an association between deficiency impaired fluid-electrolyte balance. Fluid therapy (FT), initiated 5 dpi lasted 2 weeks, fully rescued mice, restoring survival without affecting burden, immune responses, integrity. Recovered exhibited regeneration protection reinfection, demonstrating IL-22-independent pathways support long-term mucosal recovery. These findings overturn long-standing paradigm from infection, revealing primary cause mortality. Importantly, this study underscores necessity incorporating supportive therapies into preclinical models better reflect physiological conditions enhance translational relevance.

Language: Английский

Citations

1