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

J Infect Dis. 2008 Jul 15;198(2):186-92. doi: 10.1086/589305.


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 beta-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-beta-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 microg/mL for R. oryzae; 0.0625 microg/mL for other isolates) increased exposure to beta-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-beta-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 beta-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus / drug effects*
  • Aspergillus / growth & development
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / growth & development
  • Caspofungin
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Echinocandins / pharmacology*
  • Fusarium / drug effects
  • Humans
  • Hyphae / drug effects
  • Hyphae / physiology*
  • Lectins, C-Type
  • Lipopeptides
  • Membrane Proteins / genetics
  • Mycetoma / drug therapy
  • Nerve Tissue Proteins / genetics
  • Neutrophils / drug effects*
  • Neutrophils / microbiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhizopus / drug effects
  • Scedosporium / drug effects
  • Toll-Like Receptor 2 / drug effects
  • Toll-Like Receptor 4 / genetics
  • beta-Glucans / metabolism*


  • Echinocandins
  • Lectins, C-Type
  • Lipopeptides
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • beta-Glucans
  • dectin 1
  • Caspofungin