Signalling and damage pathways activated by C. albicans hyphae. C. albicans hyphal cells, when in sufficient quantities, are recognised by an unknown PRR mechanism that results in the activation of NF-B, MAPK, and PI3K pathways. MAPK signalling via p38 and ERK1/2 appears to discriminate between yeast and hyphal cells. Activation of p38 by hyphae leads to activation of the c-Fos transcription factor, which, in conjunction with the p65/p50 NF-B heterodimers and PI3K/AKT results in upregulation of cytokine and inflammatory mediator expression. Concurrently, activation of ERK1/2 signalling results in stabilisation of the MKP1 phosphatase, which deactivates p38 and JNK, hence acting as part of a negative feedback loop and preventing a potentially deleterious overreaction of the immune system. Damage induced by hyphae appears to be mediated via JNK activation and prevented via the PI3K/AKT/mTor pathway. Figure adapted from [262] and based on data from [48, 133, 134, 234, 235, 277].
