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Dysregulated neutrophil response drives lethality during Citrobacter rodentium infection in interleukin-22 deficient mice

ABSTRACT: Citrobacter rodentium (CR) is a murine enteric pathogen widely used to model attaching and effacing bacterial disease caused by enteropathogenic and enterohaemorrhagic Escherichia coli. Infection induces colonic epithelial damage and inflammation that resolves in resistant mice but results in severe disease and mortality in mice lacking interleukin-22 (IL-22). Although IL-22 promotes antimicrobial responses, epithelial barrier integrity and tissue repair during infection, the inflammatory mechanisms responsible for lethality in its absence remain poorly defined. Here, we tested whether dysregulated neutrophil responses drive disease progression in IL-22-deficient (Il22-/-) mice. Using a murine model of CR infection, we show that IL-22 deficiency is associated with progressive colonic pathology and the early emergence of a neutrophil-rich inflammatory state, characterised by markedly increased neutrophil recruitment, accumulation, and effector activity in the colonic mucosa. To determine whether excessive neutrophil responses are required for lethality, we exploited deletion of the CR type III secretion system effector EspO, a bacterial factor that promotes neutrophil recruitment. EspO deletion substantially reduced neutrophil accumulation and activity in Il22-/- mice without altering bacterial burden. Strikingly, infection with CR ΔEspO resulted in reduced colonic inflammation and 100 percent survival of infected Il22-/- mice. Together, these findings identify excessive neutrophil accumulation and activity as a key driver of lethality during CR infection in Il22-/- mice and suggest how a bacterial virulence factor amplifies neutrophil-dependent pathology within a vulnerable epithelial environment.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Graeme Benstead-Hume

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD074250 | Pride | 2026-07-08

REPOSITORIES: Pride

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			Action	DRS
	20240407_VM_Frankel_IL22KO-mice_01.raw	Raw
	20240407_VM_Frankel_IL22KO-mice_02.raw	Raw
	20240407_VM_Frankel_IL22KO-mice_03.raw	Raw
	20240407_VM_Frankel_IL22KO-mice_04.raw	Raw
	20240407_VM_Frankel_IL22KO-mice_05.raw	Raw

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Dysregulated neutrophil response drives lethality during Citrobacter rodentium infection in interleukin-22 deficient mice

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