Knowing that macrophages express a membrane form of IL-18 extends beyond NK-cell biology and into a broad spectrum of how we view and interpret IL-18. The author thanks M.

G. Netea and L. A. Joosten for helpful discussions in the preparation of this editorial. Supported by NIH Grants AI-15614, AR-45584, and CA-04 6934. The author declares no conflict of interest. “
“Clostridium sordellii causes endometrial infections, but little is known regarding host defenses against this pathogen. We tested the hypothesis that the immunoregulatory lipid prostaglandin (PG) E2 suppresses human macrophage clearance of C. sordellii through receptor-induced increases in intracellular cyclic adenosine monophosphate (cAMP). The THP-1 macrophage cell www.selleckchem.com/Proteasome.html line was used to quantify C. sordellii

phagocytosis. PGE2 increased cAMP levels, activated protein kinase A (PKA), and inhibited the class A scavenger receptor-dependent phagocytosis of C. sordellii. Activation of the EP2 this website and EP4 receptors increased intracellular cAMP and inhibited phagocytosis, with evidence favoring a more important role for EP4 over EP2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform RI appeared to be more important than RII in mediating the suppression of ingestion of C. sordellii. The endogenous lipid mediator PGE2 impairs human innate immune responses against C. sordellii. Clostridium sordellii is

an anaerobic Gram-positive bacillus that is found in the environment and is an uncommon cause of human infection. However, infections caused by toxigenic strains of C. sordellii can be severe due to the occurrence of a treatment-refractory toxic shock syndrome.[1] Women of reproductive age are at increased risk of C. sordellii infections (including endometritis) that complicate childbirth, abortion, and gynecological procedures.[2] Despite aggressive medical and surgical treatment, the mortality of C. sordellii infections has remained high.[1] The development of better therapeutic options for C. sordellii infection is limited by a lack of understanding of fundamental host–microbial interactions involved in the pathogenesis of infection. Macrophages are important sentinels of these innate immunity in the soft tissues and have been implicated as critical cellular participants in host defense against tissue-invasive clostridial infection.[3-5] It was recently reported that macrophage phagocytosis of vegetative C. sordellii was mediated by class A scavenger receptors, particularly the macrophage receptor with collagenous structure (MARCO).[6] It was also demonstrated that misoprostol, a pharmacological analog of E-series prostaglandins (PG), could impair the phagocytosis of C. sordellii by rodent macrophages.[7] This suggested that immune surveillance and clearance of C.