Granulomatous and cytokine responses to pulmonary Cryptococcus neoformans in two strains of rats

The present study was undertaken to elucidate the participation of Th1 and Th2 responses in granulomatous inflammation induced by Cryptococcus neoform ans using Lewis and Brown Norway rats which have Th1-polarized and Th2-pola rized innate immunity, respectively. Both strains demonstrated granulomatou s inflammation in the lung, and the lesions were composed mainly of mononuc lear phagocytes and surrounded by lymphocytes. Lewis rats demonstrated tube rculoid epithelioid cell granulomas with a central necrosis resembling case ation, and increased transcription of Th1 relevant cytokines. On the other hand, Brown Norway rats showed mature granulomas including eosinophils with increased transcription of IL-12 without increased transcription of not on ly IFN-gamma and IL-2 but also Th2 cytokines such as IL-4, IL-5, and IL-10, unexpectedly. The colony-forming unit of the lung was decreased exponentia lly in both strains, and that of Brown Norway rats was significantly lower than that of Lewis rats 10 days after the inoculation. This indicated that Brown Norway rats demonstrated more fungicidal activity than Lewis rats in the early stage of the infection. The role of eosinophils with humoral immu nity may be considered to be resistant in Brown Norway rats in addition of the function of macrophages.