Eosinophils are best known for their effector functions in settings of parasitic infection or allergen challenge, but have also increasingly been implicated in immune regulation at mucosal sites. Here, we show using bacterial infection and antigen challenge models that extrathymic Foxp3
+
regulatory T-cells that arise de novo in the context of bacterial infection require an intact eosinophil compartment. Mouse strains with a constitutive or conditional eosinophil deficiency, or with an eosinophil-specific ablation of
Tgfb
, lack bacterially induced neuropilin-negative, RORγt-positive gastrointestinal Treg populations in models of
Helicobacter pylori
,
Helicobacter hepaticus
and
Citrobacter rodentium
infection, as well as in the steady state colon and upon oral ovalbumin challenge. Treg priming in lymph nodes appears not to be impaired. Eosinophil-dependent tissue-resident Tregs express CTLA4, ICOS, CD39 and T-bet in addition to RORγt. Eosinophils reside in close proximity to Tregs in infected tissues, and specifically induce the expansion of newly formed Tregs, but not conventional T-cells in vivo and in vitro. TGF-β expression in eosinophils is induced by bacterial contact and during allergen exposure. Specific
Tgfb
ablation in eosinophils and the associated Treg defects result in excessive T-cell responses in the examined Th2- but not Th1-polarized settings.
Highlights d Co-infection of M. bovis and H. pylori boosts gastric Th1 responses and immunopathology d Gastric presence of H. pylori compromises immune control of M. bovis d Both mutual effects result from redirection of Treg cells to sites of M. bovis infection d CXCR3 blockade restores M. bovis control, even if H. pylori is present
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.