| Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival. | |
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MedLine Citation:
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PMID: 19451250 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. In the lungs, surfactant protein A (SP-A) and SP-D contribute to immune defense by facilitating the aggregation, uptake, and killing of many microorganisms by phagocytic cells. We hypothesized that SP-D plays a role in C. neoformans pathogenesis by binding to and enhancing the phagocytosis of the yeast. Here, the abilities of SP-D to bind to and facilitate the phagocytosis and survival of the wild-type encapsulated strain H99 and the cap59Delta mutant hypocapsular strain are assessed. SP-D binding to cap59Delta mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis of cap59Delta cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D(-/-) mice were intranasally inoculated with Alexa Fluor 488-labeled cap59Delta or H99 cells. By confocal microscopy, a greater number of phagocytosed C. neoformans cells in wild-type mice than in SP-D(-/-) mice was observed, consistent with in vitro data. Interestingly, SP-D protected C. neoformans cells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence that C. neoformans subverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy. |
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Authors:
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Scarlett Geunes-Boyer; Timothy N Oliver; Guilhem Janbon; Jennifer K Lodge; Joseph Heitman; John R Perfect; Jo Rae Wright |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-18 |
Journal Detail:
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Title: Infection and immunity Volume: 77 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-22 Completed Date: 2009-07-14 Revised Date: 2011-02-11 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 2783-94 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Colony Count, Microbial Cryptococcus neoformans / immunology* Macrophages / microbiology* Mice Mice, Inbred C57BL Mice, Knockout Microbial Viability* Phagocytosis* Protein Binding Pulmonary Surfactant-Associated Protein D / deficiency, immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI28388/AI/NIAID NIH HHS; AI42159/AI/NIAID NIH HHS; AI50184/AI/NIAID NIH HHS; AI73896/AI/NIAID NIH HHS; HL-30923/HL/NHLBI NIH HHS; HL-51134/HL/NHLBI NIH HHS; R01 HL030923-27/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Pulmonary Surfactant-Associated Protein D |
| Comments/Corrections | |
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