PXD074250

PXD074250 is an original dataset announced via ProteomeXchange.

Title	Dysregulated neutrophil response drives lethality during Citrobacter rodentium infection in interleukin-22 deficient mice
Description	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.
HostingRepository	PRIDE
AnnounceDate	2026-07-08
AnnouncementXML	Submission_2026-07-08_07:42:28.145.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-09 12:56:42	ID requested
⏵ 1	2026-07-08 07:42:28	announced

Dataset with its publication pending

submitter keyword: rodentium infection, mice,Citrobacter, interleukin-22 deficient

Jyoti Choudhary
contact affiliation	ICR, Functional Proteomics
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074250
     1. Label: PRIDE project
     2. Name: Dysregulated neutrophil response drives lethality during Citrobacter rodentium infection in interleukin-22 deficient mice