Micafungin Elicits an Immunomodulatory Effect in Galleria mellonella and Mice

Abstract

The echinocandin family of drugs is well characterized for antifungal function that inhibits β-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 Galleriamellonella model, prophylactic treatment with micafungin extended the life of Staphylococcusaureus-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 ± 6.2 % of fungal cells compared to 3.8 ± 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.