Pu Song1,2, Ge Peng1,3, Hainan Yue1,3, Takasuke Ogawa3, Shigaku Ikeda1,3, Ko Okumura1, Hideoki Ogawa1, François Niyonsaba4,5. 1. Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. 2. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, China. 3. Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan. 4. Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. francois@juntendo.ac.jp. 5. Faculty of International Liberal Arts, Juntendo University, Tokyo, Japan. francois@juntendo.ac.jp.
Abstract
PURPOSE: Although mast cells (MCs) modulate the activity of effector cells during Candida albicans infection, their role in the pathogenesis of candidiasis remains unclear. Candidalysin, a C. albicans-derived peptide toxin, is a crucial factor in fungal infections. We aimed to investigate the effect of candidalysin on MC activation and the underlying molecular mechanism. METHODS: Serum from candidalysin-immunized mice was used to measure candidalysin expression in patients infected with C. albicans. MC degranulation and migration were evaluated by β-hexosaminidase release assay and chemotaxis assay, respectively. EIA and ELISA were used to evaluate the production of eicosanoids and cytokines/chemokines, respectively. The production of nitric oxide (NO) was measured with a DAF-FM diacetate kit, while reactive oxygen species (ROS) production was analyzed by flow cytometry. MAPK activation was evaluated by Western blotting. RESULTS: We detected high candidalysin expression in the lesions of patients infected with C. albicans, and the MC number was increased in these lesions. LL-37 colocalized with MCs in the lesions of candidiasis patients. Candidalysin-enhanced MC accumulation in mice and treating LAD2 and HMC-1 cells with candidalysin induced their degranulation, migration, and production of pro- and anti-inflammatory cytokines/chemokines, eicosanoids, ROS, NO, and LL-37. Interestingly, C. albicans strains lacking candidalysin failed to induce MC activation. Moreover, candidalysin increased dectin-1 expression, and the inhibition of dectin-1 decreased MC activation. Downstream dectin-1 signaling involved the MAPK pathways. CONCLUSION: The finding that candidalysin causes cutaneous MC activation may improve our understanding of the role of MCs in the pathology of cutaneous C. albicans infection.
PURPOSE: Although mast cells (MCs) modulate the activity of effector cells during Candida albicans infection, their role in the pathogenesis of candidiasis remains unclear. Candidalysin, a C. albicans-derived peptide toxin, is a crucial factor in fungal infections. We aimed to investigate the effect of candidalysin on MC activation and the underlying molecular mechanism. METHODS: Serum from candidalysin-immunized mice was used to measure candidalysin expression in patients infected with C. albicans. MC degranulation and migration were evaluated by β-hexosaminidase release assay and chemotaxis assay, respectively. EIA and ELISA were used to evaluate the production of eicosanoids and cytokines/chemokines, respectively. The production of nitric oxide (NO) was measured with a DAF-FM diacetate kit, while reactive oxygen species (ROS) production was analyzed by flow cytometry. MAPK activation was evaluated by Western blotting. RESULTS: We detected high candidalysin expression in the lesions of patients infected with C. albicans, and the MC number was increased in these lesions. LL-37 colocalized with MCs in the lesions of candidiasis patients. Candidalysin-enhanced MC accumulation in mice and treating LAD2 and HMC-1 cells with candidalysin induced their degranulation, migration, and production of pro- and anti-inflammatory cytokines/chemokines, eicosanoids, ROS, NO, and LL-37. Interestingly, C. albicans strains lacking candidalysin failed to induce MC activation. Moreover, candidalysin increased dectin-1 expression, and the inhibition of dectin-1 decreased MC activation. Downstream dectin-1 signaling involved the MAPK pathways. CONCLUSION: The finding that candidalysin causes cutaneous MC activation may improve our understanding of the role of MCs in the pathology of cutaneous C. albicans infection.
Authors: Jonathan P Richardson; Selene Mogavero; David L Moyes; Mariana Blagojevic; Thomas Krüger; Akash H Verma; Bianca M Coleman; Jacinto De La Cruz Diaz; Daniela Schulz; Nicole O Ponde; Giulia Carrano; Olaf Kniemeyer; Duncan Wilson; Oliver Bader; Simona I Enoiu; Jemima Ho; Nessim Kichik; Sarah L Gaffen; Bernhard Hube; Julian R Naglik Journal: mBio Date: 2018-01-23 Impact factor: 7.867
Authors: David L Moyes; Duncan Wilson; Jonathan P Richardson; Selene Mogavero; Shirley X Tang; Julia Wernecke; Sarah Höfs; Remi L Gratacap; Jon Robbins; Manohursingh Runglall; Celia Murciano; Mariana Blagojevic; Selvam Thavaraj; Toni M Förster; Betty Hebecker; Lydia Kasper; Gema Vizcay; Simona I Iancu; Nessim Kichik; Antje Häder; Oliver Kurzai; Ting Luo; Thomas Krüger; Olaf Kniemeyer; Ernesto Cota; Oliver Bader; Robert T Wheeler; Thomas Gutsmann; Bernhard Hube; Julian R Naglik Journal: Nature Date: 2016-03-30 Impact factor: 49.962