Role of MKP1 in fungal disease.

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The fungal pathogen Candida albicans, the causative agent of thrush, causes millions of infections annually in people worldwide. The search for an explanation for how this fungus causes disease and immune activation has remained at the forefront of medical mycology and immunology. In recent years, we have identified a key signalling mechanism involving the phosphatase MKP1, which enables epithelial tissues to discriminate between the commensal (yeast) and pathogenic (hyphal) states of C. albicans [1]. This discriminatory mechanism is based on the host recognition of candidalysin, a cytolytic peptide toxin secreted by the fungus, and which is encoded by its parent gene ECE1 [2]. Candidalysin is produced by the hyphal form of C. albicans and is encoded by its parent gene ECE1. Ece1p is processed in the fungus to generate candidalysin, which is then secreted [3]. Candidalysin acts as a cytolytic toxin and activates host cells by inducing pores in the cell membrane. This results in the activation of a key signalling pathway involving MKP1, which is required for cytokine induction and neutrophil recruitment [4]. The phosphatase MKP1 is activated via the EGFR-ERK1/2 pathway but regulates the p38 pathway, another pathway activated by candidalysin. Importantly, candidalysin is the only damage inducing factor that C. albicans possesses. MKP1 is a phosphatase that regulates host responses via the MAPK (mitogen-activated protein kinase) pathway. In vitro, MKP1 is activated via surface receptors and cell damage caused during infection. Currently, the role of MKP1 during fungal disease is unknown.