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

T. M. Hohl, M. Feldmesser, D. S. Perlin, E. G. Pamer

Research output: Contribution to journalArticle

86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)176-185
Number of pages10
JournalJournal of Infectious Diseases
Volume198
Issue number2
DOIs
StatePublished - Jul 15 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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