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 o f the nonpathogenic yeast Saccharomyces cerevisiae was shown to be associat ed with phosphorylation of the mitogen-activated protein kinase (MAPK)/extr acellularly regulated kinase (ERK) pathway in the absence of significant ac tivation of either p38MAPK or stress-activated protein kinase/c-Jun N-termi nal kinase, However, although 80% of endocytosed C, albicans survived after 1 h, 80% of S, cerevisiae cells were killed, Considerable quantitative dif ferences were observed between the two species in the sequential phosphoryl ation 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 p hosphatase MAPK phosphatase (MKP)-1. Killing of both C, albicans and S, cer evisiae 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 macr ophages.