Some progress has been made in understanding the role of TRAIL-R1 in the immune respon

The latter pathogens include the L1,L 2,L2a, and L3 strains that infect the reticuloendothelial system involving predominantly the lymph nodes. Infection of epithelial cells by chlamydiae initiates an inflammatory response through ligation of Toll-like receptors and Nod-like receptors. These receptors are usually expressed by immune cells such as macrophages, dendritic cells and neutrophils, but also mucosal epithelial cells. The engagement of TLRs by microbial products of chlamydiae, such as lipopolysaccharide, initiates the TLR signaling cascade. Once activated, the Toll/IL-1R domain of TLR interacts with VE-821 various AbMole BioScience adaptors, such as MyD88, which in turn recruits and activates additional adaptor proteins, including the IL-1 receptor-associated kinases and -receptor-associated factor 6. TRAF6 then activates various proteins that ultimately lead to the phosphorylation of inhibitor of kappa B alpha, which subsequently undergoes degradation via ubiquitination. Clearance of infection through inflammation is often an efficient process. However, the mechanisms for clearing chlamydial infection varies among individuals whose immune systems, in addition to clearing the infection, can cause chronic inflammation. Chronic inflammation and tissue damage seen during C. trachomatis infections is caused not by the infectious organism, but by the host’s immune response to these pathogens. Therefore inflammation needs to be tightly regulated to avoid uncontrolled immune responses. Negative regulation of inflammation is accomplished at multiple levels throughout the TLR signaling pathways. The first level of regulation involves a decrease in the expression of TLR as the presence of soluble TLRs that can compete with the agonist. Soluble forms of TLR2 and TLR4 dampen the host immune response against infection by preventing the activation of TLRmediated signaling. Other regulators exert their effect within the cytosol, downstream from TLR ligation. The cytosolic regulators target different components of the TLR signaling pathway such as MyD88, IRAK1, TRAF6, and phosphoinositide 3-kinase. The transmembrane receptor of TNF-related apoptosis-inducing ligand receptor is a member of the tumor necrosis factor receptor superfamily that lacks a TIR domain. In addition to its well-established role in inducing apoptosis, TRAILR has been reported to modulate inflammation of the host cells in response to various pathogens and diseases. Four different TRAIL-Rs have been identified in humans and one full-length receptor in mice. TRAIL-R1 and TRAIL-R2, also known as Death Receptor -4 and DR-5, are the only known receptors that are capable of selectively killing transformed cells but not normal cells, while TRAIL-R3 and TRAIL-R4 serve as decoys. TRAIL-R-deficient mice develop normal populations of immune cells, but challenge of these mice with different pathogens and stimuli for TLR2, TLR3 and TLR4 results in enhanced ability of the innate immune system to clear the infection and increased production of different pro-inflammatory-cytokines such as IFN-b, compared to wildtype mice. The ability of TRAIL-R to downregulate TLR signaling seems to be through decrease activation of NF-kB by stabilizing the I-kBa subunit. While murine TRAIL-R is established as a negative regulator of inflammation.

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