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...

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Bibliographic Details
Published in:Medical mycology (Oxford) 2008-11, Vol.46 (7), p.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: Article
Language:English
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
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Summary: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
ISSN:1369-3786
1460-2709
DOI:10.1080/13693780801982762