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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Movement / genetics
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Cell Movement / immunology
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Cryptococcosis / genetics
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Cryptococcosis / immunology*
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Cryptococcosis / mortality
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Cryptococcosis / pathology
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Cryptococcus neoformans / growth & development
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Cryptococcus neoformans / immunology*
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Immunity, Innate
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Lung Diseases, Fungal / genetics
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Lung Diseases, Fungal / immunology
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Lung Diseases, Fungal / mortality
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Lung Diseases, Fungal / pathology
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Meningitis, Cryptococcal / genetics
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Meningitis, Cryptococcal / immunology
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Meningitis, Cryptococcal / mortality
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Meningitis, Cryptococcal / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Organ Specificity / genetics
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Organ Specificity / immunology
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Receptors, CCR5 / biosynthesis
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Receptors, CCR5 / deficiency
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Receptors, CCR5 / genetics
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Receptors, CCR5 / physiology*
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Th1 Cells / immunology
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Th1 Cells / metabolism