title: Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis.
abstract: We hypothesized that the ability of BCG vaccination to protect against Mycobacterium tuberculosis is less in hosts exposed to chronic helminthes infection compared to unexposed individuals. To test this hypothesis we evaluated the efficacy of BCG vaccination in protecting against M. tuberculosis challenge in Schistosoma mansoni pre-infected mice by analyzing their ability to limit the replication of TB bacilli in the lung and liver and the histology of lung sections. The results show that BCG vaccinated mice with prior S. mansoni infection show significantly higher number of colony forming units of TB bacilli as well as significant reduction in air exchange area in the lung compared to controls. In addition, spleen cells from S. mansoni infected mice were found to produce significantly less IFN-gamma and nitric oxide when stimulated in vitro with PPD and several fold higher soluble egg antigen (SEA) and Concanavalin A induced IL-4 and IL-5 secretion. Taken together, our data show that S. mansoni infection reduces the protective efficacy of BCG vaccination against M. tuberculosis possibly by attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, 17177 Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Elias
authors.forename: Hannah
authors.initials: H
authors.lastname: Akuffo
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlowski
authors.forename: Melles
authors.initials: M
authors.lastname: Haile
authors.forename: Thomas
authors.initials: T
authors.lastname: Schön
authors.forename: Sven
authors.initials: S
authors.lastname: Britton
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D002908:Chronic Disease; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000150:complications / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014376:Tuberculosis / Q000150:complications / Q000276:immunology* / Q000473:pathology
chemical_list: D001500:BCG Vaccine; D015848:Interleukin-5; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma