title: Prior exposure to live Mycobacterium bovis BCG decreases Cryptococcus neoformans-induced lung eosinophilia in a gamma interferon-dependent manner.
abstract: Some common childhood infections appear to prevent the development of atopy and asthma. In some Mycobacterium bovis BCG-vaccinated populations, strong delayed-type hypersensitivity responses to mycobacterial antigens are associated with a reduced risk of atopy. Although BCG exposure decreases allergen-induced lung eosinophilia in animal models, little attention has been given to the effect of immunity to BCG on responses against live pathogens. We used the murine Cryptococcus neoformans infection model to investigate whether prior BCG infection can alter such responses. The present study shows that persistent pulmonary BCG infection of C57BL/6 mice induced an increase in gamma interferon, a reduction in interleukin-5, and a decrease in lung eosinophilia during subsequent Cryptococcus infection. This effect was long lasting, depended on the presence of live bacteria, and required persistence of mycobacterial infection in the lung. Reduction of eosinophilia was less prominent after infection with a mutant BCG strain (DeltahspR), which was rapidly cleared from the lungs. These observations have important implications for the development of vaccines designed to prevent Th2-mediated disease and indicate that prior lung BCG vaccination can alter the pattern of subsequent host inflammation.
authors.affiliation: Centre for Molecular Microbiology and Infection, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Ian R
authors.initials: IR
authors.lastname: Humphreys
authors.forename: Ben G
authors.initials: BG
authors.lastname: Marshall
authors.forename: Lorna
authors.initials: L
authors.lastname: Edwards
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Openshaw
authors.forename: Rory J
authors.initials: RJ
authors.lastname: Shaw
authors.forename: Tracy
authors.initials: T
authors.lastname: Hussell
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003453:Cryptococcosis / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011657:Pulmonary Eosinophilia / Q000517:prevention & control*; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma