Surfactant protein D binding to Aspergillus fumigatus hyphae is calcineurin-sensitive.

Journal Article (Journal Article)

Surfactant protein D (SP-D) plays a central role in pulmonary innate immune responses to microbes and allergens, often enhancing clearance of inhaled material. Although SP-D functions during bacterial and viral infections are well established, much less is known about its possible roles during invasive fungal infections. Aspergillus fumigatus is a prominent fungal pathogen in immunocompromised individuals, and can cause allergic or invasive aspergillosis. SP-D has been shown to be protective against both of these disease modalities. The moieties present on the fungal surface responsible for SP-D binding remain largely unclear, although cell wall 1,3-beta-D-glucan is bound by SP-D in other fungal species. There is little information regarding the interaction of SP-D with A. fumigatus hyphae which are responsible for the invasive form of disease. Here, we show that SP-D binding to A. fumigatus hyphae is sensitive to the activity of the calcium-activated protein phosphatase calcineurin. Deletion of the catalytic subunit calcineurin A (DeltacnaA) or pharmacologic inhibition of calcineurin through FK506 abrogated SP-D binding. In contrast, SP-D binding to Cruptococcus neoformans was calcineurin-independent. Pharmacologic inhibition of A. fumigatus cell wall components by caspofungin (inhibits 1,3-beta-D-glucan synthesis) and nikkomycin Z (inhibits chitin synthesis) increased SP-D binding to the wild-type strain. In contrast, SP-D binding increased in the DeltacnaA strain only after nikkomycin Z treatment. We conclude that SP-D binding to A. fumigatus hyphae is calcineurin-sensitive, presumably as a consequence of calcineurin's role in regulating production of key cell wall binding partners, such as 1,3-beta-D-glucan. Elucidation of the interaction between lung innate immune factors and A. fumigatus could lead to the development of novel therapeutic interventions.

Full Text

Duke Authors

Cited Authors

  • Geunes-Boyer, S; Heitman, J; Wright, JR; Steinbach, WJ

Published Date

  • June 2010

Published In

Volume / Issue

  • 48 / 4

Start / End Page

  • 580 - 588

PubMed ID

  • 20141481

Pubmed Central ID

  • PMC3676939

Electronic International Standard Serial Number (EISSN)

  • 1460-2709

Digital Object Identifier (DOI)

  • 10.3109/13693780903401682


  • eng

Conference Location

  • England