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.
Huffnagle
G B
GB
Pulmonary Division, Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA. ghuff@umich.edu
McNeil
L K
LK
McDonald
R A
RA
Murphy
J W
JW
Toews
G B
GB
Maeda
N
N
Kuziel
W A
WA
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003453:Cryptococcosis / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000276:immunology*; D007113:Immunity, Innate; D008172:Lung Diseases, Fungal / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D016919:Meningitis, Cryptococcal / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D019713:Receptors, CCR5