PROTECTIVE ROLE OF GAMMA-INTERFERON IN EXPERIMENTAL PULMONARY PARACOCCIDIOIDOMYCOSIS

We have developed a murine model of pulmonary infection by Paracoccidi oides brasiliensis in which resistance was associated with immunologic al activities governed by gamma interferon (IFN-gamma). To better char acterize this model, we measured type 1 and type 2 cytokines in the lu ngs and investigated the effect of endogenous IFN-gamma depletion by m onoclonal antibodies in the course of infection of susceptible (B10.A) and resistant (A/Sn) mice, At weeks 4 and 8 after infection, lungs fr om susceptible animals presented levels of IFN-gamma, interleukin-4 (I L-4), IL-5, and IL-10 higher than those in resistant mice, In both mou se strains, neutralization of endogenous IFN-gamma induced exacerbatio n of the pulmonary infection, earlier fungal dissemination to the live r and spleen, impairment of the specific cellular immune response resu lting in significantly lower delayed-type hypersensitivity reactions, and increased levels of immunoglobulin G1 (IgG1)- and IgG2b-specific a ntibodies, Histopathological analysis demonstrated that depletion of I FN-gamma changes the focal granulomatous lesions found in the lungs of B10.A and A/Sn mice into coalescent granulomata which destroy the pul monary architecture, These results suggest that irrespective of the mo use strain, IFN-gamma plays a protective role and that this cytokine i s one major mediator of resistance against P. brasiliensis infection i n mice.