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 Cryptococcu s neoformans, 12-wk survival was >90% for CCR5(+/+) mice but <25% far CCR5( -/-) mice. There were no defects in lung leukocyte recruitment (wk 5), pulm onary clearance, or delayed-type hypersensitivity in CCR5(-/-) mice. Howeve r, CCR5(-/-) mice had defects in leukocyte recruitment into the brain and, strikingly, in elimination of cryptococcal polysaccharide from the brain. I n nonimmune CCR5(-/-) mice, there was a significant defect in macrophage re cruitment after challenge with shed cryptococcal products (C, neoformans fi ltrate Ag) but not other nonspecific stimuli. Thus, CCR5 plays specific rol es in innate immunity and organ-specific leukocyte trafficking during host defense against C. neoformans.