Cryptococcosis in beige mice: the effect of congenital defects in innate immunity on susceptibility

The influence of the beige (bg/bg) mutation on susceptibility to cryptococcosis was assessed by mortality, quantitative culturing, and histopathology of infected organs from bg/bg and bg/+ mice. Immunodeficient bg/bg mice were more susceptible to systemic cryptococcosis than immunocompetent bg/+ mice. Differences in susceptibility of bg/bg and bg/+ mice corresponded with temporal differences in histopathology. In contrast to bg/+ mice, inflammatory responses in infected tissues from bg/bg mice contained less cellular infiltrate, proportionally more polymorphonuclear neutrophils than monocytes and macrophages, and delays in the switch from acute to chronic inflammation. Enhanced growth of Cryptococcus neoformans in the internal organs of bg/bg mice was coincident with delayed inflammatory responses. These quantitative culture and histopathology studies suggest that the defects associated with monocytes and macrophages and polymorphonuclear neutrophils resulted in altered in vivo inflammatory responses and contributed to the enhanced susceptibility of beige mice to C. neoformans.