Caspofungin modulates inflammatory responses to Aspergillus fumigatus through stage-specific effects on fungal β-glucan exposure Journal Article

   

Authors:	Hohl, T. M.; Feldmesser, M.; Perlin, D. S.; Pamer, E. G.
Article Title:	Caspofungin modulates inflammatory responses to Aspergillus fumigatus through stage-specific effects on fungal β-glucan exposure
Abstract:	Echinocandins target fungal β-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 micafungin-treated 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 TNF and CXCL2 by macrophages and demonstrated intense staining with a 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. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Keywords:	controlled study; nonhuman; drug targeting; animal cell; mouse; microscopy, confocal; inflammation; in vitro study; drug effect; morphology; tumor necrosis factor-alpha; drug mechanism; staining; immunomodulation; receptor; macrophage; cytokine release; cxcl2 chemokine; antibody; caspofungin; antifungal agents; echinocandin; beta 1,3 glucan; dectin 1; aspergillus fumigatus; candida albicans; conidium; fungus hyphae; aspergillosis; micafungin; fungus growth; beta-glucans; tumor necrosis factor; antifungal activity; macrophage activation; dectin 1 receptor; chemokine cxcl2; echinocandins
Journal Title:	Journal of Infectious Diseases
Volume:	198
Issue:	2
ISSN:	0022-1899
Publisher:	Oxford University Press
Date Published:	2008-07-15
Start Page:	176
End Page:	185
Language:	English
DOI:	10.1086/589304
PUBMED:	18500928
PROVIDER:	scopus
PMCID:	PMC2587116
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-47649089027&partnerID=40&md5=79f1a8057a84a34706c081d8a6764e73
Notes:	--- - "Cited By (since 1996): 35" - "Export Date: 17 November 2011" - "CODEN: JIDIA" - "Source: Scopus"

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