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The goal of this work was to evaluate the activity of macrophages and T cells in murine experimental models of paracoccidioidomycosis using High (H) and Low (L) antibody-producer mice of the IV-A selection, and to explain the differences in the pattern of pulmonary lesions showed by both strains. Animals were intravenously infected with 18 strains of P. brasiliensis (2.0 x 105 yeast/animal) and sacrificed after 3 days, and 1, 2, and 4 weeks. The following parameters were observed: recovery of viable fungi from pulmonary lesions; lymphocytes proliferative response to Concanavalin A (Con A); INF-γ determination in the serum and in the supernatant of spleen cells culture; and H2O2, NO, and TNF-α release by peritoneal macrophages. HIV-A mice had a higher recovery of viable fungi from the lung in the beginning of the infection (3 days and 1 week) when compared with LIV-A. This was inverted in the last periods of time, and LIV-A showed a higher recovery of fungi. With regards to the lymphocytes proliferative response, there was a positive association between the higher recovery of fungi in the HIV-A strain and the lower proliferative response only after 3 days and 1 week. Higher levels of INF-γ were remarkably related to lower recovery of fungi in the HIV-A animals. With respect to the activation state of macrophages, the higher production of H2O2 in the HIV-A strain after 3 days was associated to a control of the fungi multiplication in the lung. On the other hand, the decrease in this metabolite production in the LIV-A strain was associated to an increase in the recovery of fungi. NO production was increased in HIV-A strain when these animals showed lower recovery of fungi, but this association cannot be made in the LIV-A. Another indicative of macrophage activation was TNF-α production. This cytokine level was high in the beginning of the infection in both strains. However, this increase cannot be associated to a possible control of fungi multiplication, mainly in the HIV-A strain, when the increase of this cytokine was associated to a higher fungi recovery. Thus, the higher levels of TNF-α showed by the infected animals, when compared to controls, were considered as a parameter of macrophage activation and not as a regulatory cytokine involved in fungi multiplication. Our results show the important role of INF-γ in the defense mechanisms against P. brasiliensis.

the journal of venomous animals and toxins including tropical diseases

Evaluation of macrophages and T cells activity in murine experimental models of high and low antibody-producers (selection IV-A) infected with Paracoccidioides brasiliensis