Protective Role of Gamma Interferon in Experimental Pulmonary Paracoccidioidomycosis |
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| Authors: | Luz E. Cano, Suely S. Kashino, Celina Arruda, Denise Andr , Cynthia F. Xidieh, Lucia M. Singer-Vermes, Celid ia A. C. Vaz, Eva Burger, Vera L. G. Calich |
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| Affiliation: | Luz E. Cano, Suely S. Kashino, Celina Arruda, Denise André, Cynthia F. Xidieh, Lucia M. Singer-Vermes, Celidéia A. C. Vaz, Eva Burger, and Vera L. G. Calich |
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| Abstract: | We have developed a murine model of pulmonary infection by Paracoccidioides brasiliensis in which resistance was associated with immunological activities governed by gamma interferon (IFN-γ). To better characterize this model, we measured type 1 and type 2 cytokines in the lungs and investigated the effect of endogenous IFN-γ depletion by monoclonal antibodies in the course of infection of susceptible (B10.A) and resistant (A/Sn) mice. At weeks 4 and 8 after infection, lungs from susceptible animals presented levels of IFN-γ, interleukin-4 (IL-4), IL-5, and IL-10 higher than those in resistant mice. In both mouse strains, neutralization of endogenous IFN-γ induced exacerbation of the pulmonary infection, earlier fungal dissemination to the liver and spleen, impairment of the specific cellular immune response resulting in significantly lower delayed-type hypersensitivity reactions, and increased levels of immunoglobulin G1 (IgG1)- and IgG2b-specific antibodies. Histopathological analysis demonstrated that depletion of IFN-γ changes the focal granulomatous lesions found in the lungs of B10.A and A/Sn mice into coalescent granulomata which destroy the pulmonary architecture. These results suggest that irrespective of the mouse strain, IFN-γ plays a protective role and that this cytokine is one major mediator of resistance against P. brasiliensis infection in mice. |
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