Surfactant protein D binding to Aspergillus fumigatus hyphae is calcineurin-sensitive.
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.
Geunes-Boyer
Scarlett
S
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Heitman
Joseph
J
Wright
Jo Rae
JR
Steinbach
William J
WJ
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D001228:Aspergillosis / Q000276:immunology / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000378:metabolism*; D016466:CHO Cells; D019703:Calcineurin / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003455:Cryptococcus neoformans / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D025301:Hyphae / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology
D000617:Aminoglycosides; D037663:Pulmonary Surfactant-Associated Protein D; C011952:nikkomycin; D019703:Calcineurin; D016559:Tacrolimus