Role of extracellular signal-regulated protein kinase cascade in macrophage killing of Candida albicans.
The pathogenic yeast Candida albicans and its derived molecules stimulate a wide range of macrophage secretory functions and may adapt to escape being killed by this phagocyte. In this study, phagocytosis of C. albicans and of the nonpathogenic yeast Saccharomyces cerevisiae was shown to be associated with phosphorylation of the mitogen-activated protein kinase (MAPK)/extracellularly regulated kinase (ERK) pathway in the absence of significant activation of either p38MAPK or stress-activated protein kinase/c-Jun N-terminal kinase. However, although 80% of endocytosed C. albicans survived after 1 h, 80% of S. cerevisiae cells were killed. Considerable quantitative differences were observed between the two species in the sequential phosphorylation of MAPK/ERK kinase (MEK), extracellularly regulated kinase-1, and 90-kDa-ribosomal S6 kinases. A lower level of activation of the pathway by C. albicans was associated with a species-specific overexpression of the MEK phosphatase MAPK phosphatase (MKP)-1. Killing of both C. albicans and S. cerevisiae could be reduced using PD98059, which mimics MKP-1 and inhibits MEK phosphorylation, suggesting that specific MKP-1 activation by C. albicans could contribute to its ability to escape the yeast lytic potential of macrophages.
Ibata-Ombetta
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Laboratoire de Mycologie Fondamentale et Appliquée, INSERM EPI 9915, Université de Lille II, Faculté de Médecine H. Warembourg, Pôle Recherche, 59037 Lille Cedex, France.
Jouault
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Trinel
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Poulain
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D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D018797:Cell Cycle Proteins; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000276:immunology; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000276:immunology; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D017874:Immediate-Early Proteins; D019893:Ribosomal Protein S6 Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one