Prostaglandin signaling suppresses innate defense functions of monocytes and macrophages. In this depiction, the prostaglandins PGE₂ and prostacyclin (PGI₂) trigger the intracellular production of the second messenger cAMP through the activation of G_s-coupled receptors on monocytes or macrophages. PGE₂ evokes cAMP through EP2 and EP4 receptors while PGI₂ does so through the IP receptor. cAMP-signaling cascades impair 3 primary functions of these innate immune cells: phagocytosis, intracellular killing, and the induction of inflammatory mediators (cytokines, chemokines, and lipids) by cells infected with bacterial pathogens. NF-κB, the transcription factor nuclear factor κB; and PRR, pathogen recognition receptor (eg, Toll-like receptors). Red bars indicate inhibitory signaling pathways.