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(Journal of Leukocyte Biology. 2001;70:149-154.)
© 2001 by Society for Leukocyte Biology

Role of extracellular signal-regulated protein kinase cascade in macrophage killing of Candida albicans

Stella Ibata-Ombetta, Thierry Jouault, Pierre-André Trinel and Daniel Poulain

Laboratoire de Mycologie Fondamentale et Appliquée, INSERM EPI 9915, Université de Lille II, Faculté de Médecine H. Warembourg, Pôle Recherche, 59037 Lille Cedex, France

Correspondence: Thierry Jouault, Laboratoire de Mycologie Fondamentale et appliquée, Université de Lille II, Faculté de Médecine H. Warembourg, Pôle Recherche, Place Verdun, 59037 Lille Cedex, France. E-mail: tjouault{at}univ-lille2.fr

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.

Key Words: MAP kinases • phagocytosis • yeast • pathogenicity • macrophages




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