Figure 10. Proposed mechanisms involved in zymosan uptake and signaling in human macrophages.

Zymosan particles can activate Syk via dectin-1 engagement and through the adaptor protein DAP12. After internalization into phagosomes, TLR2 recognition and cathepsin B leakage may occur. In the presence of M-CSF, the expression of dectin-1 B isoform is increased and allows for an enhanced receptor-dependent binding. If the LPS/TLR4 cascade is activated, an additional, concomitant mechanism of NF-κB activation will be triggered. cPLA₂ is activated by dectin-1/Syk-dependent mechanisms involving MAPK-dependent Ser-505 phosphorylation and Ca²⁺-dependent membrane translocation, whereas the induction of COX-2 depends mainly on κB-dependent transcriptional regulation. IFNγ signaling leads to the activation of the promoter of the inducible microsomal isoform of prostaglandin E synthase (pges) by an IFN-stimulated response element (ISRE)-dependent or GAS (interferon-γ activated sequence)-dependent mechanism. The dotted lines indicate the steps associated with phagocytic cargo processing. Ac-H3 indicates acetylated histone H3.