IL-10 Production in Macrophages Is Regulated by a TLR-Driven CREB-Mediated Mechanism That Is Linked to Genes Involved in Cell Metabolism

摘要: IL-10 is produced by macrophages in diverse immune settings and critical limiting immune-mediated pathology. In helminth infections, are an important source of IL-10; however, the molecular mechanism underpinning production these cells poorly characterized. this study, bone marrow–derived exposed to excretory/secretory products released Schistosoma mansoni cercariae rapidly produce as a result MyD88-mediated activation MEK/ERK/RSK p38. The phosphorylation kinases was triggered TLR2 TLR4 converged on transcription factor CREB. Following phosphorylation, CREB recruited novel regulatory element Il10 promoter also responsible for regulating network genes involved metabolic processes, such glycolysis, tricarboxylic acid cycle, oxidative phosphorylation. Moreover, skin-resident tissue macrophages, which encounter S. during infection, first monocytes vivo early postinfection with cercariae. rapid release has potential condition dermal microenvironment encountered infection site, we propose regulates skin, but major effect their state.