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MRx0518 acts on both the innate and adaptive immune system to induce a unique response mediated by TLR5.
Intimate adherence by enteropathogenic Escherichia coli modulates TLR5 localization and proinflammatory host response in intestinal epithelial cells.
Conversely, certain receptors for bacterial-derived products may have a protective role in the progression of inflammation; indeed, it has been observed that the specific deletion of TLR5 and TLR7 promotes the inflammatory pathways.
Al-Attas et al., "A nonsense polymorphism (R392X) in TLR5 protects from obesity but predisposes to diabetes," Journal of Immunology, vol.
NOX1 is expressed in the colon and the vascular system and can be triggered by flagellin, via TLR5 , by LPS via TLR4 , and by CpG oligonucleotides via TLR9  and is sensitive to IFN[gamma] .
Additionally, some toll like receptors including TLR1, TLR2, TLR4, TLR5 and TLR6 recognize bacteria (Iwasaki and Medzhitov, 2004).
(1) Depending on their cellular localization or respective PAMPs they identify, TLRs can be divided into two sub groups such as transmembrane (TLR1, TLR2, TLR4, TLR5, TLR6, and TLR11) and intracellular (TLR3, TLR7, TLR8, and TLR9).
One group is composed of TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10, which are expressed on cell surfaces and recognize microbial membrane components such as lipids, lipoproteins, and proteins; the other group is composed of TLR3, TLR7, TLR8, and TLR9, which are expressed exclusively in intracellular vesicles, and they recognize microbial nucleic acids (Cario, 2005).
This effect of nano-vaccination strategy (with TLR5 agonists) also varies on different parameters of the immune system; in this regard, the cellular immune responses had a higher stimulation level compared with the humoral immune responses.
This includes activation of Toll-like receptor 4 (Tlr4) by lipopolysaccharide and Toll-like receptor 5 (Tlr5) by bacterial flagellin.
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