Anticryptococcal Activity of Macrophages: Role of Mouse Strain, C5, Contact, Phagocytosis, and L-Arginine

The antifungal activity of nonactivated resident murine peritoneal macrophages for Cryptococcus neoformans was studied. Macrophages from five of six mouse strains tested had significant (40 to 80%) fungistatic activity, depending on the inoculum size, in a 24-hr coculture system. Macrophages from two outbred (SW and ICR) and three inbred (BALB/c, C57B1/6, and DBA/2J) strains were fungistatic. Only macrophages from outbred CD-1 mice lacked fungistatic activity. Heat-inactivated and C5-deficient sera did not support phagocytosis or fungistasis by resident BALB/c or DBA/2 macrophages. Fungistasis correlated with contact, complement, and phagocytosis. Macrophages were studied in a Lab-Tek chamber slide system where noningested cells were washed away. Fungistasis in this system was similar to that found with a microtest plate coculture method where a smaller inoculum was cultured continuously with macrophages. After ingestion of yeast cells, CD-1 macrophages could be activated for fungistasis (70%) with interferon-γ plus lipopolysaccharide. Activated BALB/c macrophages had increased fungistasis but were not fungicidal. NG-Monomethyl-L-alginine (200 μM), which inhibited the fungistatic activity of activated CD-1 macrophages, did not inhibit inherent fungistatic activity of BALB/c macrophages. The fungistatic mechanism of BALB/c macrophages resembled that reported for resident human macrophages.