Caspofungin-mediated β-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae

Gregory A. Lamaris, Russell E. Lewis, Georgios Chamilos, Gregory S. May, Amar Safdar, Thomas J. Walsh, Issam I. Raad, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticle

Abstract

Background. We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage. Materials and methods. Using aniline blue staining, we compared patterns of β-glucan exposure in Aspergillus fumigatus, Aspergillus terreus, Rhizopus oryzae, Fusarium solani, Fusarium oxysporum, Scedosporium prolificans, and Scedosporium apiospermum hyphae after caspofungin exposure. We also determined PMN-mediated hyphal damage occurring with or without preexposure to caspofungin or with preexposure to the combination of caspofungin and anti-β-glucan monoclonal antibody, using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-sH- tetrazolium hydroxide (XTT) assay. Results. Preincubation with caspofungin (32 μg/mL for R. oryzae; 0.0625 μg/mL for other isolates) increased exposure to β-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-β-glucan antibody. Preincubation with micafungin or anidulafungin had similar effects on PMN-induced damage of A. fumigatus hyphae. Finally, preexposure of A. fumigatus, but not S. prolificans, to caspofungin induced expression of Dectin-1 by PMN. Conclusions. The results of the present study suggest inducement of β-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.

Original languageEnglish (US)
Pages (from-to)186-192
Number of pages7
JournalJournal of Infectious Diseases
Volume198
Issue number2
DOIs
StatePublished - Jul 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Lamaris, G. A., Lewis, R. E., Chamilos, G., May, G. S., Safdar, A., Walsh, T. J., Raad, I. I., & Kontoyiannis, D. P. (2008). Caspofungin-mediated β-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae. Journal of Infectious Diseases, 198(2), 186-192. https://doi.org/10.1086/589305