title: Deficiency of IL-12p40 subunit determines severe paracoccidioidomycosis in mice.
abstract: Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. To investigate the role of interleukin (IL)-12 in this disease, IL-12p40-/- deficient mice (IL-12p40-/-) and wild type mice (WT) were infected intravenously with viable yeast cells of P. brasiliensis 18 isolate. We found that, unlike WT mice, IL-12p40-/- mice did not control fungal proliferation and dissemination and succumbed to infection by day 21 after inoculation. Additionally, IL-12p40-/- mice presented a higher number of granulomas/mm2 in lung tissue than WT mice, and showed unorganized granulomas containing high numbers of yeast cells. Moreover, IL-12p40-/- mice did not release detectable levels of IFN-gamma, but they produced high levels of IL-10, as well as IgG1 antibody. Additionally, splenocytes from both infected IL-12p40-/- and WT mice exhibited a suppressed Con-A-induced T cell proliferative response. Our findings suggest that the IL-12p40 subunit mediates resistance in paracoccidioidomycosis by inducting IFN-gamma production and a Th1 immune response.
authors.affiliation: Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. mclivonesi@yahoo.com.br
authors.forename: Marcia Cristina
authors.initials: MC
authors.lastname: Livonesi
authors.forename: Janeusa Trindade
authors.initials: JT
authors.lastname: Souto
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campanelli
authors.forename: Claudia M Leite
authors.initials: CM
authors.lastname: Maffei
authors.forename: Roberto
authors.initials: R
authors.lastname: Martinez
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Rossi
authors.forename: Joao Santana
authors.initials: JS
authors.lastname: Da Silva
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D049109:Cell Proliferation; D015169:Colony Count, Microbial; D005260:Female; D015745:Granuloma, Foreign-Body / Q000382:microbiology / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency* / Q000235:genetics*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D016753:Interleukin-10; D007371:Interferon-gamma