Cutting edge: role of CC chemokine receptor 5 in organ-specific and innate immunity to Cryptococcus neoformans

GB Huffnagle, LK McNeil, RA McDonald… - The Journal of …, 1999 - journals.aai.org
GB Huffnagle, LK McNeil, RA McDonald, JW Murphy, GB Toews, N Maeda, WA Kuziel
The Journal of Immunology, 1999journals.aai.org
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 …
Abstract
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.
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