Fungistatic and fungicidal activities of murine polymorphonuclear leucocytes against yeast cells of Paracoccidioides brasiliensis

Recently, a novel culture medium for detecting live yeast cells of Paracocc idioides brasiliensis was developed by Kurita et al. Using this culture med ium, murine peritoneal polymorphonuclear leucocytes (PMN) were examined for fungistatic and fungicidal activities against P. brasiliensis yeast cells. The magnitude of the antifungal effect of PMN varied depending upon the fu ngal isolates used. PMN exhibited a killing effect on P. brasiliensis isola te Bt-4 in 2 h of coculture. In contrast, the other three fungal isolates e mployed were resistant to killing by PMN. However, PMN considerably suppres sed the growth of isolates Tatu and Recife in a long-term assay (similar to 72 h). The growth of isolate Bt-9 was also suppressed by PMN during the fi rst 24 h, but was found to be considerably promoted at 72 h of coculture. I nterferon-gamma (IFN-gamma), but not tumour-necrosis factor-alpha, signific antly augmented the antifungal activity of PMN. IFN-gamma-treated PMN exhib ited a killing effect on isolates Tatu, Recife and Bt-9 after 24 h of cocul ture, and showed an enhanced killing effect on isolate Bt-4. Contact betwee n PMN and fungal cells was required for PMN to exert the antifungal effect. Our results suggest that PMN, whether activated with cytokines or not, mig ht play a critical role in host resistance in early infection with this fun gus by buying time for development of more effective immunologic responses.