Colonic bacterial infection abrogates eosinophilic pulmonary disease

Induction of immunity to one pathogen in the lungs modifies the microenvironment and alters immunopathological changes that result from a second, unrelated pulmonary infection. However, it is unclear whether immunity generated at distant sites also affects lung immune responses. Here, we show that infection with the gut-restricted bacterium Citrobacter rodentium modifies immunopathological changes that result from pulmonary Cryptococcus neoformans infection. Th2 cytokine-driven pulmonary eosinophilia induced by C. neoformans infection was reduced, and the enhanced Th1 cytokine environment afforded more-rapid clearance of the fungus in C. rodentium-immune mice. The activated and intraepithelial (CD103+) T cell populations that expand after C. neoformans infection were diminished in C. rodentium-immune mice. T cell cross-reactivity was absent, but cross-reactive antibodies were detected. It is of importance to the "hygiene hypothesis" that these data indicate that an immune response induced by a gut-restricted pathogen can modify the immune outcome after pulmonary infection, suggesting that cell-phenotype modifications occur across mucosal sites.