Deficiency of IL-12p40 subunit determines severe paracoccidioidomycosis in mice

• Published in: Medical mycology (Oxford) Vol. 46; no. 7; pp. 637 - 646
• Main Authors: Livonesi, Márcia Cristina, Souto, Janeusa Trindade, Campanelli, Ana Paula, Leite Maffei, Cláudia M., Martinez, Roberto, Rossi, Marcos A., Silva, João Santana Da
• Format: Journal Article
• Language: English
• Published: UK Informa UK Ltd 01-11-2008
• Subjects: Animals; Antibodies, Fungal - blood; Cell Proliferation; Colony Count, Microbial; Female; Granuloma, Foreign-Body - microbiology; Granuloma, Foreign-Body - pathology; Immunoglobulin G - metabolism; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-12 Subunit p40 - deficiency; Interleukin-12 Subunit p40 - genetics; Lung - immunology; Lung - microbiology; Lung - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Paracoccidioides - immunology; Paracoccidioidomycosis - genetics; Paracoccidioidomycosis - immunology; Paracoccidioidomycosis - mortality; Paracoccidioidomycosis - pathology; Spleen - immunology; Spleen - microbiology; Survival Analysis; T-Lymphocytes - cytology; T-Lymphocytes - immunology; IL-12; immunosuppression; granulomas
• ISSN: 1369-3786; 1460-2709
• DOI: 10.1080/13693780801982762

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- , 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- production and a Th1 immune response