Cutting edge: Role of C-C chemokine receptor 5 in organ-specific and innate immunity to Cryptococcus neoformans.

After intratracheal inoculation of the AIDS-associated pathogen Cryptococcus neoformans, 12-wk survival was >90% for CCR5+/+ mice but <25% for CCR5-/- mice. There were no defects in lung leukocyte recruitment (wk 5), pulmonary clearance, or delayed-type hypersensitivity in CCR5-/- mice. However, CCR5-/- mice had defects in leukocyte recruitment into the brain and, strikingly, in elimination of cryptococcal polysaccharide from the brain. In nonimmune CCR5-/- mice, there was a significant defect in macrophage recruitment after challenge with shed cryptococcal products (C. neoformans filtrate Ag) but not other nonspecific stimuli. Thus, CCR5 plays specific roles in innate immunity and organ-specific leukocyte trafficking during host defense against C. neoformans.