Deficiency of IL-12p40 subunit determines severe paracoccidioidomycosis in mice.
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.
Livonesi
Marcia Cristina
MC
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. mclivonesi@yahoo.com.br
Souto
Janeusa Trindade
JT
Campanelli
Ana Paula
AP
Maffei
Claudia M Leite
CM
Martinez
Roberto
R
Rossi
Marcos A
MA
Da Silva
Joao Santana
JS
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
D000908:Antibodies, Fungal; D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D016753:Interleukin-10; D007371:Interferon-gamma