A (64%) and A/J (75%) mice. In this study, we evaluated the in situ localization of IFN-γ in the granulomatous response developed in the omentum of mice infected with P. brasiliensis. Herein,

the immunohistochemical evaluation allowed us to detect the presence of IFN-γ only in cells with lymphomononuclear morphology. Immunostained cells were located mainly at the periphery of the granulomas circumscribing macrophages, epithelioid cells, and giant cells around fungi in the center of the lesions. Other authors also demonstrated the presence of IFN-γ positive cells in cutaneous lesions of human PCM, and it was correlated to well-organized granulomas and maintenance of cellular immune response (Pagliari & Sotto, 2003). At 15 days after infection, the similar presence in both Afatinib supplier number of positive cells and intensity of IFN-γ staining detected in susceptible and resistant mice confirms earlier data that at this

time of infection the genetic background of susceptibility and resistance is not manifested yet (Fazioli et al., 1994). On the other hand, at later phase of infection, resistant mice showed a higher IFN-γ staining in lymphomononuclear cells compared with susceptible mice, suggesting the presence of protective immune mechanisms to the control of fungal dissemination through the high activation status of phagocytes, as previously described (Calich et al., 1994). Therefore, susceptible mice although able to produce IFN-γ since the early stage of the infection, could not control the fungal dissemination, as demonstrated by the several loose granulomas Metformin containing viable fungal cells, indicating their incapacity to control the infection, and confirmed by the higher fungal load in omentum lesions of B10.A than in A/J mice previously observed by the same authors (Nishikaku et al., 2008). Cellular distribution of IFN-γ was similar in mice infected with the slightly virulent isolate Pb265, showing positive immunostaining localized

at the periphery of the lesions in both mouse strains. Quantitative analysis demonstrated that IFN-γ positive cells were observed in both mouse strains at the early phase of Pb265 infection, but differently from the infection with the highly virulent Pb18 in which their positivity was increased; infection with Pb265 was associated with the presence of residual Cyclooxygenase (COX) lesions with lower number of IFN-γ positive cells, suggesting the inactivation of inflammatory/immune reaction and the resolution of the infection. The presence of IFN-γ has been observed in necrotic processes (Sugawara et al., 1998), whereas TGF-β has been associated with fibrosis in the granulomatous lesions (Wynn, 2004). In previous studies using the murine model of PCM, TNF-α (Nishikaku, 2003), and TGF-β (Nishikaku & Burger, 2003a) immunostaining was detected in macrophages and multinucleated giant cells, as well as in ECM components.