Impaired Host Defense against Sporothrix schenckii in Mice with Chronic Granulomatous Disease

Abstract

ABSTRACT We compared the immune defense of mice with chronic granulomatous disease (CGD mice) with that of wild-type C57BL/6 mice for their response to Sporothrix schenckii . A subcutaneous injection of 5 × 10 4 CFU S. schenckii strain IFM41598 into CGD mice resulted in systemic infection and death within 84 days. In contrast, injected C57BL/6 mice did not develop systemic infection and were able to survive through 100 days of observation. Differences in host resistance were analyzed in vitro. Neutrophils and macrophages obtained from CGD mice were found to allow greater growth of this organism than did those obtained from C57BL/6 mice. Moreover, macrophages obtained from immunized CGD mice were able to simply inhibit the growth of this fungus whereas macrophages obtained from immunized C57BL/6 mice killed the fungus within 48 h after phagocytosis. These results suggest that (i) the lack of NADPH oxidase function is a risk factor for lethal S. schenckii infection and (ii) superoxide anion and its reactive oxidative metabolites produced by neutrophils and macrophages are involved in fungistatic and fungicidal activities.