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Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival.
- Source :
-
Infection and immunity [Infect Immun] 2009 Jul; Vol. 77 (7), pp. 2783-94. Date of Electronic Publication: 2009 May 18. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Animals
Cell Line
Colony Count, Microbial
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Binding
Pulmonary Surfactant-Associated Protein D deficiency
Pulmonary Surfactant-Associated Protein D metabolism
Cryptococcus neoformans immunology
Macrophages microbiology
Microbial Viability
Phagocytosis
Pulmonary Surfactant-Associated Protein D immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 77
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 19451250
- Full Text :
- https://doi.org/10.1128/IAI.00088-09