Caspofungin‐Mediated β‐Glucan Unmasking and Enhancement of Human Polymorphonuclear Neutrophil Activity againstAspergillusand Non‐AspergillusHyphae
Open Access
- 15 July 2008
- journal article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 198 (2), 186-192
- https://doi.org/10.1086/589305
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.Keywords
This publication has 34 references indexed in Scilit:
- Changing patterns and trends in systemic fungal infectionsJournal of Antimicrobial Chemotherapy, 2005
- Role of anti-β-glucan antibody in host defense against fungiFEMS Immunology & Medical Microbiology, 2005
- Innate Immunity to the Pathogenic Fungus Coccidioides posadasii Is Dependent on Toll-Like Receptor 2 and Dectin-1Infection and Immunity, 2005
- Combined action of micafungin, a new echinocandin, and human phagocytes for antifungal activity against Aspergillus fumigatusMicrobes and Infection, 2004
- The Antifungal Drug Amphotericin B Promotes Inflammatory Cytokine Release by a Toll-like Receptor- and CD14-dependent MechanismJournal of Biological Chemistry, 2003
- Impact of current transplantation practices on the changing epidemiology of infections in transplant recipientsThe Lancet Infectious Diseases, 2003
- A new receptor for β-glucansNature, 2001
- A Microtiter-Based Fluorescence Assay for (1,3)-β-Glucan SynthasesAnalytical Biochemistry, 1997
- A Simplified New Assay for Assessment of Fungal Cell Damage with the Tetrazolium Dye, (2,3)-bis-(2-Methoxy-4-Nitro-5-Sulphenyl)-(2H)-Tetrazolium-5-Carboxanilide (XTT)The Journal of Infectious Diseases, 1995
- Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activities against (1,3)-beta-D-glucan synthaseAntimicrobial Agents and Chemotherapy, 1994