title: Natural transmission of Plasmodium berghei exacerbates chronic tuberculosis in an experimental co-infection model.
abstract: Human populations are rarely exposed to one pathogen alone. Particularly in high incidence regions such as sub-Saharan Africa, concurrent infections with more than one pathogen represent a widely underappreciated public health problem. Two of the world's most notorious killers, malaria and tuberculosis, are co-endemic in impoverished populations in the tropics. However, interactions between both infections in a co-infected individual have not been studied in detail. Both pathogens have a major impact on the lung as the prime target organ for aerogenic Mycobacterium tuberculosis and the site for one of the main complications in severe malaria, malaria-associated acute respiratory distress syndrome (MA-ARDS). In order to study the ramifications caused by both infections within the same host we established an experimental mouse model of co-infection between Mycobacterium tuberculosis and Plasmodium berghei NK65, a recently described model for MA-ARDS. Our study provides evidence that malaria-induced immune responses impair host resistance to Mycobacterium tuberculosis. Using the natural routes of infection, we observed that co-infection exacerbated chronic tuberculosis while rendering mice less refractory to Plasmodium. Co-infected animals presented with enhanced inflammatory immune responses as reflected by exacerbated leukocyte infiltrates, tissue pathology and hypercytokinemia accompanied by altered T-cell responses. Our results--demonstrating striking changes in the immune regulation by co-infection with Plasmodium and Mycobacterium--are highly relevant for the medical management of both infections in humans.
authors.affiliation: Department of Infectious Diseases, Parasitology Unit, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Mueller
authors.forename: Jochen
authors.initials: J
authors.lastname: Behrends
authors.forename: Kristine
authors.initials: K
authors.lastname: Hagens
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mahlo
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Schaible
authors.forename: Bianca E
authors.initials: BE
authors.lastname: Schneider
mesh_terms: D000818:Animals; D002908:Chronic Disease; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010962:Plasmodium berghei / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma