Virulence of fungi: correlation of virulence of Blastomyces dermatitidis in vivo with escape from macrophage inhibition of replication in vitro

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Abstract
Strains of Blastomyces dermatitidis which are virulent (V), attenuated (A), or avirulent (AV) in mice have been identified. Virulence of V has been reported to be associated with its ability to replicate in vivo, causing lethal infections in the lungs or in the peritoneal cavity. We report here that V, but not A or AV, has the ability to replicate in vivo in nonlethal subcutaneous lesions. The possibility that V was able to replicate in vivo by evading primary host defenses was investigated. We studied the interaction of macrophages and strains of B. dermatitidis in vitro. In 24-h cocultures, the replication of all three strains of B. dermatitidis was inhibited by macrophages from: (i) untreated mice (20 to 40%), (ii) mice that had recovered from nonlethal blastomycosis (40 to 60%), (iii) concanavalin A-treated mice (50 to 70%), or (iv) peritoneal exudates elicited by thioglycolate (65 to 80%). However, at 72 h in the first three types of cocultures A and AV remained inhibited, whereas V was not inhibited (0 to 4%). Only the most inhibitory macrophages, those induced by thioglycollate, inhibited V at 72 h, though V was again less inhibited than A or AV at that time. Thus, we show a correlation between virulence of V in vivo and its ability to escape from macrophage inhibition of replication in vitro.