INGESTION OF CANDIDA-ALBICANS DOWN-REGULATES MANNOSE RECEPTOR EXPRESSION ON RAT MACROPHAGES

The frequency of infection and death due to various Candida species ha s increased steadily during the past decade, with mucocutaneous candid al infections as a common problem in the immunocompromised host. Monon uclear phagocytes are important in phagocytosis of this organism. In a reas where there are low levels of opsonins, the macrophage-specific m annose receptor plays a dominant role in mediating Candida albicans in gestion. Following receptor-mediated infection, the host macrophage pr oduces inflammatory cytokines and mediators that lead to ultimate kill ing of the invading Candida. Infection of macrophages by pathogens oft en leads to altered function that might effect their subsequent host d efense properties. For example, function of both the complement recept or type 3 and the mannose receptor are down-regulated following exposu re to pathogens or pathogen-derived products, In the current study, we have examined the down-regulation of mannose receptor expression foll owing Candida infection and have investigated possible mechanisms that might be involved, Mannose receptor activity was decreased following 24 h postinfection with Candida. Both tumor necrosis factor and nitric oxide were produced during the infection, and inhibition of the these mediators partially blocked the effect on the receptor, Infection wit h Candida also inhibited the ability of dexamethasone to up-regulate m annose receptor expression. Finally, mannose receptor protein turnover was accelerated in Candida-infected macrophages. We conclude that Can dida downregulates one of the receptors involved in its internalizatio n through a combination of production of modulatory molecules and enha nced receptor degradation. These results support the hypothesis that p athogens that infect macrophages have the ability to alter the phagocy tic pathways available for subsequent host defense. (C) 1997 Academic Press.