Nuclear factor-kappa B activation and innate immune response in microbial pathogen infection

Human pathogenic microorganisms have developed a variety of strategies to i nfect the host organism successfully, whereas the host has evolved a series of defense mechanisms. In most cases, the epithelial cell layer represents the first barrier for the bacterial pathogen and triggers the innate and i nflammatory responses in the host. Epithelial cells release proinflammatory mediators including cytokines and chemokines, leading to the subsequent at traction of monocytes/macrophages. Therefore, epithelial cells represent an immediate-early warning system in the host organism. Subsequent to the col onization of the epithelial layer, invasive microbial pathogens often induc e an acute inflammatory response, which functions to activate residential m acrophages and recruits blood leukocytes to the site of infection. Distinct receptors of the Toll family on the cell surface of immune cells mediate a ntibacterial responses in mammals as well as in Drosophila. One of the most important cellular factors involved in the regulation of the host innate a ntimicrobial response is the immediate-early response transcription factor nuclear factor (NF)-kappa B. Microbial pathogens activate cellular signal t ransduction pathways that induce NF-kappa B activation, but pathogens also find ways to overcome the innate immune response through active manipulatio n of the NF-kappa B signal transduction pathways. Exploration of the mechan isms that influence NF-kappa B activity could contribute to a better unders tanding of the molecular pathogenesis of microbial infections and could be important for potential therapeutic intervention that may be relevant in a wide variety of inflammatory diseases. BIOCHEM PHARMACOL 60;8:1109-1114, 20 00. (C) 2000 Elsevier Science Inc.