Other cell types. We covered four main conclusions. OSU-03012 PDK-1 inhibitor First, the human neuronal cells possess TLR3, functional TLR4, RIG-I and MDA5 PRR signaling pathways whose T was ACTION maturation mediated dependent Dependent. Second, both induced extracellular And re-transfected poly potent IFN-induction in β neurons to autocrine activation of ISRE. Third, neurons innate antiviral pathways mediated immune TLR3, RIG-I and MDA5 are non-Peltier et al. Page 11 J. Immunol Author manuscript, increases available in PMC 15th June 2011. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript redundant and preferred to respond to different ligands. Fourth, perhaps MDA5 and TLR3-mediated reactions are up-regulated by neuronal PI3K, and in particular the PI3K p110 subunit.
These results show that human neuronal cells, a relatively big e complement-mediated PRR have innate immune system means, and there This usually means that are by viral pathogens by nucleic acid recognition protein stimulates most active. Previous studies on the PRR signaling pathways in neurons of the central nervous system have OSU-03012 742112-33-0 focused on M Opportunities TLRmediated focus and examines their impact on various aspects of the physiology of the brain, including normal development and regeneration. Several studies have examined the r The TLR3 in response to viral infections of the CNS, although the R M Possible antiviral TLR3-mediated signaling pathways is controversial and may be pathogen specific. For example, people adversely Chtigt TLR3 genetic Pr Disposition for herpes simplex virus encephalitis, but TLR3 � � Mice have a decreased susceptibility to rabies virus encephalitis.
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In contrast to TLR3, induced neuronal innate immune response and MDA5 are cytosolic PRR Rigi less well studied. The expression of both RIG-I or MDA5 could be induced by IFN β WNV infection in neurons or mouse cortical culture, but basal expression was not detected by immunoblot. Although we also found that both type I IFN were overexpressed RLRS treatment of human neurons, we found basal expression, particularly in differentiated cells. In addition, we found that both routes RIG-I and MDA5-mediated active in human neural cells were. The presence of innate immune functions of the cytosolic PRRactivated pathways in neurons, it is not surprising, because the innate antiviral response to several neurotropic viruses has been shown that RIG-I linked to and / or MDA5 pathways providing non-neuronal cells.
However, this may be the result of his reactions Differ significantly between neuronal and non-neuronal cells, the mature CNS neurons are essentially irreplaceable Able and thus initiation of the apoptotic cascade can be entered altruistic k Can irreversibly Sch To have the dinner hour In spite of preventing the spread of the virus at the same time. An interesting hypothesis is that neuronal responses PRR, potentially increased Ht or modulated in other CNS-resident cells such as astrocytes or microglia, viral replication team of professionals from PRR-initiated reactions and f Promote the social survival of neurons, either by signaling pathways previously not recognized or uncharacterized. accordance with this hypothesis suggest vorl INDICATIVE results suggest that the neurotropic virus activates western equine encephalitis virus is an alpha prosurvival IRF3-dependent ngigen pathway in human neuronal C