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Biochemistry Research Paper

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Toll-like receptors are proteins that play a significant role in the recognition of pathogens such as viruses and bacteria, thereby initiating an innate response. The TLR family recognizes structurally conserve molecules known as pathogen-associated molecular patterns (PAMPS) derive from these viruses and bacteria. TLR7 have been shown to mediate the recognition of single stranded RNA (ssRNA) viruses, whereas TLR9 recognizes non-methylated CpG sequences in bacterial DNA molecules. However, the molecular mechanism by which non-methylated CpG DNA and ssRNA viruses activate the innate immunity is not well understood. In this paper, it is demonstrated that the cell response to vesicular stomatitis viruses (VSV) and bacteria DNA is mediated by TLR7 and TLR9. Through the generation of TLR7 and TLR9-deficient mice, it was determined that TLR7 are required for responsiveness to both vesicular stomatitis viruses and TLR9 recognizes bacteria DNA. Both TLR7 and TLR9 deficient mice did not show any response to single stranded RNA viruses and non-methylated CpG bacteria DNA including inflammatory cytokine production from macrophages and dendritic cells. However, the in vivo ability of vesicular stomatitis viruses and CpG bacteria DNA to stimulate IL-12 secretion depended on the functional activation of MyD88 and IRAK. These results present evidence for the requirement of TLR7 for single stranded RNA viruses and TLR9 for non-methylated CpG bacteria DNA to induced cellular effects. Conversely, further results provide evidence that support the role for TLR7 and TLR9 to trigger vesicular stomatitis viruses and CpG bacteria DNA mediated signaling transduction resulting in the induction of the interferon response [266]. Introduction: The inna... ... middle of paper ... ... bone marrow of WT, TLR7,TLR9, or MyD88 deficient mice and infected with VSV for 18hrs. IFN and IL-12 level were determined from culture supernatant by ELISA Lund, J.M.et al Conclusion: In justification with the previous study on TLR9 recognition of CpG DNA and initiating an innate immune system, Lund, J.M. et al have demonstrated that, together, TLR7 and TLR9 likely form a functional subgroup within the TLR family that recognize pathogen-associated molecular pattern (PAMPS) in endosomal compartment. It is now clear TLR7 and TLR9 play a significant role in the recognition of vesicular stomatitis virus and CpG bacteria DNA, thereby activating the innate immune system. The experiments with TLR7 and TLR9 deficient mice have shown the essential role in the recognition of ssRNA by TLR7 and non-methylated CpG bacteria DNA by TLR9 respectively.
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