TITLE

Caspofungin Modulates Inflammatory Responses to Aspergillus fumigatus through Stage-Specific Effects on Fungal ß-Glucan Exposure

AUTHOR(S)
Hohl, T. M.; Feldmesser, M.; Perlin, D. S.; Pamer, E. G.
PUB. DATE
July 2008
SOURCE
Journal of Infectious Diseases;7/15/2008, Vol. 198 Issue 2, p176
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Echinocandins target fungalβ-1,3 glucan synthesis and are used clinically to treat invasive aspergillosis. Although echinocandins do not completely inhibit in vitro growth of Aspergillus fumigatus, they do induce morphological changes in fungal hyphae. Because β-1,3 glucans activate host antifungal pathways via the Dectin-1 receptor, we investigated the effect of echinocandins on inflammatory responses to A. fumigatus. Caspofungin- or micafungintreated conidia and germlings induced less secretion of tumor necrosis factor (TNF) and CXCL2 by macrophages than did their untreated counterparts. Diminished secretion of TNF and CXCL2 correlated with diminished β-glucan exposure on echinocandin-treated germ tubes. In contrast to treated conidia and germlings, echinocandin-treated hyphae stimulated increased release of TNFandCXCL2by macrophages and demonstrated intense staining with β-glucan-specific antibody, particularly at hyphal tips. Our experiments demonstrate that echinocandin-induced morphological changes in A. fumigatus hyphae are accompanied by increased β-glucan exposure, with consequent increases in Dectin-1-mediated inflammatory responses by macrophages.
ACCESSION #
33114342

 

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