期刊
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
卷 201, 期 1, 页码 93-101出版社
SPRINGER
DOI: 10.1007/s00430-011-0209-y
关键词
Candida albicans; Candida dubliniensis; Hypha formation; MAPK; MKP1; c-Fos; NF-kappa B; Oral epithelium; Innate immunity
资金
- NIDCR [DE017514]
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
- Wellcome Trust Value In People (VIP)
- FEMS
- King's College London
Oral epithelial cells detect the human pathogenic fungus Candida albicans via NF-kappa B and a bi-phasic mitogen-activated protein kinase (MAPK) signaling response. However, discrimination between C. albicans yeast and hyphal forms is mediated only by the MAPK pathway, which constitutes activation of the MAPK phosphatase MKP1 and the c-Fos transcription factor and is targeted against the hyphal form. Given that C. albicans is not the only Candida species capable of filamentation or causing mucosal infections, we sought to determine whether this MAPK/MKP1/c-Fos mediated response mechanism was activated by other pathogenic Candida species, including C. dubliniensis, C. tropicalis, C. parapsilosis, C. glabrata and C. krusei. Although all Candida species activated the NF-kappa B signaling pathway, only C. albicans and C. dubliniensis were capable of inducing MKP1 and c-Fos activation, which directly correlated with hypha formation. However, only C. albicans strongly induced cytokine production (G-CSF, GM-CSF, IL-6 and IL-1 alpha) and cell damage. Candida dubliniensis, C. tropicalis and C. parapsilosis were also capable of inducing IL-1 alpha and this correlated with mild cell damage and was dependent upon fungal burdens. Our data demonstrate that activation of the MAPK/MKP1/c-Fos pathway in oral epithelial cells is specific to C. dubliniensis and C. albicans hyphae.
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