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Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival.

Publication ,  Journal Article
Geunes-Boyer, S; Oliver, TN; Janbon, G; Lodge, JK; Heitman, J; Perfect, JR; Wright, JR
Published in: Infect Immun
July 2009

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.

Duke Scholars

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

July 2009

Volume

77

Issue

7

Start / End Page

2783 / 2794

Location

United States

Related Subject Headings

  • Pulmonary Surfactant-Associated Protein D
  • Protein Binding
  • Phagocytosis
  • Microbiology
  • Microbial Viability
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Cryptococcus neoformans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Geunes-Boyer, S., Oliver, T. N., Janbon, G., Lodge, J. K., Heitman, J., Perfect, J. R., & Wright, J. R. (2009). Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival. Infect Immun, 77(7), 2783–2794. https://doi.org/10.1128/IAI.00088-09
Geunes-Boyer, Scarlett, Timothy N. Oliver, Guilhem Janbon, Jennifer K. Lodge, Joseph Heitman, John R. Perfect, and Jo Rae Wright. “Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival.Infect Immun 77, no. 7 (July 2009): 2783–94. https://doi.org/10.1128/IAI.00088-09.
Geunes-Boyer S, Oliver TN, Janbon G, Lodge JK, Heitman J, Perfect JR, et al. Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival. Infect Immun. 2009 Jul;77(7):2783–94.
Geunes-Boyer, Scarlett, et al. “Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival.Infect Immun, vol. 77, no. 7, July 2009, pp. 2783–94. Pubmed, doi:10.1128/IAI.00088-09.
Geunes-Boyer S, Oliver TN, Janbon G, Lodge JK, Heitman J, Perfect JR, Wright JR. Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival. Infect Immun. 2009 Jul;77(7):2783–2794.

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

July 2009

Volume

77

Issue

7

Start / End Page

2783 / 2794

Location

United States

Related Subject Headings

  • Pulmonary Surfactant-Associated Protein D
  • Protein Binding
  • Phagocytosis
  • Microbiology
  • Microbial Viability
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Cryptococcus neoformans