title: 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 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 ± 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.
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Aldrich 708, POB 328/330, Providence, RI, USA. helen_fuchs@brown.edu.
authors.forename: Beth Burgwyn
authors.initials: BB
authors.lastname: Fuchs
authors.affiliation: Pharmacy Department, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, General Hospital of Chinese PLA, Beijing, China.
authors.forename: Dedong
authors.initials: D
authors.lastname: Li
authors.affiliation: The Miriam Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Johnston
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Aldrich 708, POB 328/330, Providence, RI, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Hendricks
authors.affiliation: Department of Laboratory Medicine, Jinshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Aldrich 708, POB 328/330, Providence, RI, USA.
authors.forename: Rajmohan
authors.initials: R
authors.lastname: Rajamuthiah
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Aldrich 708, POB 328/330, Providence, RI, USA. emylonakis@lifespan.org.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D054714:Echinocandins / Q000008:administration & dosage* / Q000494:pharmacology*; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000494:pharmacology*; D007915:Lepidoptera; D055666:Lipopeptides / Q000008:administration & dosage* / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D000077551:Micafungin; D051379:Mice; D050296:Microbial Viability; D013203:Staphylococcal Infections / Q000188:drug therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D054714:Echinocandins; D007155:Immunologic Factors; D055666:Lipopeptides; D000077551:Micafungin
keywords: Candida albicans; Echinocandins; Galleria mellonella; Immunomodulatory; Micafungin