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Surfactant Protein D enhances phagocytosis of Cryptococcus neoformans hypocapsular strain cap59Δ by murine macrophages
Author(s) -
GeunesBoyer Scarlett Gabriel,
Oliver Timothy N,
Heitman Joseph,
Perfect John R,
Wright Jo Rae
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.674.14
Subject(s) - cryptococcus neoformans , phagocytosis , microbiology and biotechnology , cryptococcosis , innate immune system , biology , immune system , in vitro , surfactant protein d , immunology , biochemistry
Cryptococcus neoformans is an opportunistic pathogen and the leading cause of fungal meningitis in humans. Infection occurs following inhalation of C. neoformans cells, which, in the absence of a cellular immune response, results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan (GXM), which makes up approximately 90% of the capsular material. In the lungs, surfactant proteins SP‐A and SP‐D contribute to innate defense by facilitating the aggregation, uptake and killing of microorganisms by phagocytic cells. We hypothesized that SP‐D plays a role in C. neoformans pathogenesis by facilitating its clearance. We examined the ability of SP‐D to modulate the innate immune response to C. neoformans serotype A using wild type encapsulated strain H99 and mutant hypocapsular strain cap59Δ. We assessed the ability of SP‐D to bind to and facilitate phagocytosis of both C. neoformans strains. We found that SP‐D binds to cap59Δ approximately six‐fold better than to H99, and enhances phagocytosis of cap59Δ about four‐fold in vitro. To investigate SP‐D binding in vivo, SP‐D−−/− mice were intranasally instilled with AF488‐labeled cap59Δ. We observed a greater number of phagocytosed C. neoformans cells in wild type compared to SP‐D−/− mice, consistent with our in vitro data, using confocal microscopy. These studies suggest that SP‐D plays a role in host defense against C. neoformans by binding to and enhancing its phagocytosis. This work was supported by NIH grant HL‐30923