FIGURE 12.

Pathways regulating induction of immediate early genes in C. albicans-infected RPM. C. albicans infection of RPM rapidly stimulates activation of MAPKs and calcium increases through MyD88-, Dectin-1-, and Dectin-2-mediated pathways. ERKs and p38 phosphorylate cPLA₂α, which enhances catalytic activity, and calcium binds to the C2 domain, which promotes translocation to the Golgi and the phagosome. Arachidonic acid released by cPLA₂α is metabolized by constitutively expressed COX-1 to PGI₂ and PGE₂. COX-1 is an integral membrane protein primarily localized in the endoplasmic reticulum but is also found in the Golgi. Binding of PGI₂ to the IP receptor and of PGE₂ to the EP2 and EP4 receptors increases cAMP and activation of PKA, which acts synergistically with p38-dependent CREB phosphorylation, resulting in induction of Ptgs2, Nr4a2, and Il10 and suppression of Tnfα. AA, arachidonic acid.