Micafungin Elicits an Immunomodulatory Effect in Galleria mellonella and Mice

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• 作者：Beth Burgwyn Fuchs ; Yan Li ; Dedong Li ; Tatiana Johnston…
• 关键词：Candida albicans ; Echinocandins ; Galleria mellonella ; Immunomodulatory ; Micafungin
• 刊名：Mycopathologia
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：181
• 期：1-2
• 页码：17-25
• 全文大小：599 KB
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• 作者单位：Beth Burgwyn Fuchs (1)
  Yan Li (2)
  Dedong Li (3)
  Tatiana Johnston (4)
  Gabriel Hendricks (1)
  Gang Li (5)
  Rajmohan Rajamuthiah (1)
  Eleftherios Mylonakis (1)
  
  1. Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Aldrich 708, POB 328/330, Providence, RI, USA
  2. Pharmacy Department, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, China
  3. Department of Clinical Pharmacology, General Hospital of Chinese PLA, Beijing, China
  4. The Miriam Hospital, Alpert Medical School of Brown University, Providence, RI, USA
  5. Department of Laboratory Medicine, Jinshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Microbiology
  Medical Microbiology
  Plant Sciences
  Microbial Ecology
  
• 出版者：Springer Netherlands
• ISSN：1573-0832

文摘

The echinocandin family of drugs is well characterized for antifungal function that inhibits 尾-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鈥檚 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 卤 6.2 % of fungal cells compared to 3.8 卤 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. Keywords Candida albicans Echinocandins Galleria mellonella Immunomodulatory Micafungin