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.
Williams
Andrew E
AE
Kennedy Institute of Rheumatology, Charing Cross Campus, Imperial College, London, United Kingdom.
Edwards
Lorna
L
Hussell
Tracy
T
D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D000954:Antigens, Surface / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D044082:Citrobacter rodentium / Q000276:immunology; D003092:Colitis / Q000150:complications* / Q000276:immunology* / Q000382:microbiology; D003429:Cross Reactions; D003453:Cryptococcosis / Q000150:complications* / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011657:Pulmonary Eosinophilia / Q000150:complications* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000908:Antibodies, Fungal; D000954:Antigens, Surface