Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival
| Autor: | John R. Perfect, Guilhem Janbon, Timothy N. Oliver, Scarlett Geunes-Boyer, Jennifer K. Lodge, Joseph Heitman, Jo Rae Wright |
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| Rok vydání: | 2009 |
| Předmět: |
Phagocytosis
Immunology Colony Count Microbial Microbiology Cell Line Mice Immune system Macrophage Animals Pulmonary Surfactant-Associated Protein D Cryptococcus neoformans Mice Knockout Microbial Viability biology Intracellular parasite Macrophages Surfactant protein D biology.organism_classification Surfactant protein A Mice Inbred C57BL Infectious Diseases Parasitology Fungal and Parasitic Infections Protein Binding |
| Zdroj: | Infection and immunity. 77(7) |
| ISSN: | 1098-5522 |
| Popis: | Cryptococcus neoformansis 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 ofC. neoformanscells or spores results in pulmonary infection.C. neoformanscells 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 inC. neoformanspathogenesis 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 thecap59Δ mutant hypocapsular strain are assessed. SP-D binding tocap59Δ mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis ofcap59Δ cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D−/−mice were intranasally inoculated with Alexa Fluor 488-labeledcap59Δ or H99 cells. By confocal microscopy, a greater number of phagocytosedC. neoformanscells in wild-type mice than in SP-D−/−mice was observed, consistent with in vitro data. Interestingly, SP-D protectedC. neoformanscells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence thatC. neoformanssubverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy. |
| Databáze: | OpenAIRE |
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