Caspofungin-mediated beta-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae.
BACKGROUND
We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage.


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.
Lamaris
Gregory A
GA
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Lewis
Russell E
RE
Chamilos
Georgios
G
May
Gregory S
GS
Safdar
Amar
A
Walsh
Thomas J
TJ
Raad
Issam I
II
Kontoyiannis
Dimitrios P
DP
D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D054714:Echinocandins / Q000494:pharmacology*; D005670:Fusarium / Q000187:drug effects; D006801:Humans; D025301:Hyphae / Q000187:drug effects / Q000502:physiology*; D037181:Lectins, C-Type; D055666:Lipopeptides; D008565:Membrane Proteins / Q000235:genetics; D008271:Mycetoma / Q000188:drug therapy; D009419:Nerve Tissue Proteins / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012233:Rhizopus / Q000187:drug effects; D021681:Scedosporium / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics; D047071:beta-Glucans / Q000378:metabolism*; D000099181:Dectin-1
D000077336:Caspofungin; D054714:Echinocandins; D037181:Lectins, C-Type; D055666:Lipopeptides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D047071:beta-Glucans; D000099181:Dectin-1