Journal
MYCOPATHOLOGIA
Volume 181, Issue 1-2, Pages 17-25Publisher
SPRINGER
DOI: 10.1007/s11046-015-9940-z
Keywords
Candida albicans; Echinocandins; Galleria mellonella; Immunomodulatory; Micafungin
Categories
Funding
- Astellas
- Natural Science Grant of China [81102480]
- Brown-Brazil Initiative
- NIH [T-32DA013911]
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The echinocandin family of drugs is well characterized for antifungal function that inhibits beta-d-glucan synthesis. The aim of this work was to study whether micafungin, a member of the echinocandin family, elicits additional activities that prime the host's immune response. We found that in a Galleria mellonella model, prophylactic treatment with micafungin extended the life of Staphylococcus aureus-infected larvae (a pathogen to which the drug demonstrates no direct antimicrobial activity) compared to insects that did not receive micafungin (P < 0.05). The inhibition of pathogens in the G. mellonella infection model was characterized by a 2.43-fold increase in hemocyte density, compared to larvae inoculated with PBS. In a murine model where animals were provided micafungin prophylaxis 3 days prior to macrophage collection, macrophages were found associated with an average 0.9 more fungal cells per macrophage as compared to saline-treated animals. Interestingly, micafungin-stimulated macrophages killed 11.6 +/- A 6.2 % of fungal cells compared to 3.8 +/- A 2.4 % of macrophages from saline-treated animals. The prophylactic provision of micafungin prior to Candida albicans infection was characterized by an increase in the proinflammatory cytokines CXCL13 and SPP1 by 11- and 6.9-fold, respectively. In conclusion, micafungin demonstrated the ability to stimulate phagocytic cells and promote an immune response that can inhibit microbial infections.
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