Epithelial GM-CSF induction by Candida glabrata.
The main cytokine induced by the interaction of oral epithelial cells with C. glabrata is granulocyte monocyte colony-stimulating factor (GM-CSF); however, the mechanisms regulating this response are unknown. Based on previously published information on the interactions of C. albicans with oral epithelial cells, we hypothesized that interaction with viable C. glabrata triggers GM-CSF synthesis via NF-kappaB activation. We found that C. glabrata-induced GM-CSF synthesis was adhesion-dependent, enhanced by endocytosis, and required fungal viability. NF-kappaB activation was noted during interaction of epithelial cells with C. glabrata, and pre-treatment with an NF-kappaB inhibitor partly inhibited GM-CSF synthesis. Blocking TLR4 with anti-TLR4 antibody did not inhibit GM-CSF production. In contrast, an anti-CDw17 antibody triggered significant inhibition of NF-kappaB activation and GM-CSF synthesis. beta-glucans did not stimulate GM-CSF synthesis, suggesting that the CDw17/NF-kappaB/GM-CSF pathway may be beta-glucan-independent. This study provides new insights into the mechanism of GM-CSF induction by C. glabrata.
Li
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Division of Periodontology, School of Dental Medicine, University of Connecticut, 263 Farmington Ave., Farmington, CT 06030-1710, USA.
Dongari-Bagtzoglou
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D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D041221:Candida glabrata / Q000276:immunology* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D015638:Cytochalasin D / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D005936:Glucans; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007790:Lactosylceramides / Q000037:antagonists & inhibitors / Q000276:immunology; D009061:Mouth Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011134:Polysaccharides / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000276:immunology; D015054:Zymosan / Q000276:immunology; D047071:beta-Glucans / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D005936:Glucans; D007790:Lactosylceramides; D016328:NF-kappa B; D019384:Nucleic Acid Synthesis Inhibitors; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D047071:beta-Glucans; C069894:poly-1-6-glucopyranosyl-1-3-glucopyranose glucan; D015638:Cytochalasin D; C009744:CDw17 antigen; C038459:curdlan; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C008247:laminaran; D015054:Zymosan