Microglia are brain immune cells responsible for immune surveillance. Microglial activation is, however, closely associated with neuroinflammation, neurodegeneration, and obesity. Therefore, it is... Show moreMicroglia are brain immune cells responsible for immune surveillance. Microglial activation is, however, closely associated with neuroinflammation, neurodegeneration, and obesity. Therefore, it is critical that microglial immune response appropriately adapts to different stressors. The circadian clock controls the cellular process that involves the regulation of inflammation and energy hemostasis. Here, we observed a significant circadian variation in the expression of markers related to inflammation, nutrient utilization, and antioxidation in microglial cells isolated from mice. Furthermore, we found that the core clock gene-Brain and Muscle Arnt-like 1 (Bmal1) plays a role in regulating microglial immune function in mice and microglial BV-2 cells by using quantitative RT-PCR. Bmal1 deficiency decreased gene expression of pro-inflammatory cytokines, increased gene expression of antioxidative and anti-inflammatory factors in microglia. These changes were also observed in Bmal1 knock-down microglial BV-2 cells under lipopolysaccharide (LPS) and palmitic acid stimulations. Moreover, Bmal1 deficiency affected the expression of metabolic associated genes and metabolic processes, and increased phagocytic capacity in microglia. These findings suggest that Bmal1 is a key regulator in microglial immune response and cellular metabolism. Show less
Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic... Show moreMyeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of these cells is mammalian target of rapamycin (mTOR). During infection, pathogens use host metabolic pathways to scavenge host nutrients, as well as target metabolic pathways for subversion of the host immune response that together facilitate pathogen survival. Given the pivotal role of mTOR in controlling metabolism and DC and macrophage function, pathogens have evolved strategies to target this pathway to manipulate these cells. This review seeks to discuss the most recent insights into how pathogens target DC and macrophage metabolism to subvert potential deleterious immune responses against them, by focusing on the metabolic pathways that are known to regulate and to be regulated by mTOR signaling including amino acid, lipid and carbohydrate metabolism, and autophagy. Show less
Smolders, V.F.; Zodda, E.; Quax, P.H.A.; Carini, M.; Barbera, J.A.; Thomson, T.M.; ... ; Cascante, M. 2019
