Title page for etd-0712114-024747


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URN etd-0712114-024747
Author Pei-yi Su
Author's Email Address No Public.
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Department Biological Sciences
Year 2013
Semester 2
Degree Master
Type of Document
Language zh-TW.Big5 Chinese
Title The role of TLR8 on Mycobacterium tuberculosis infection
Date of Defense 2014-07-16
Page Count 102
Keyword
  • polymorphism
  • PMA
  • THP-1 cells
  • TLR8
  • Mycobacterium tuberculosis (Mtb)
  • Abstract Tuberculosis (TB) has recently re-emerged as a major global public health threat and Mycobacterium tuberculosis (Mtb) is a highly successful pathogen that evolved remarkable strategies to establish persistent infection. There is strong evidence that host genetic factors influence individual susceptibility to TB. We have demonstrated that the frequency of the TLR8 -129C allele was higher in male patients with pulmonary TB than in healthy controls (24.1% vs. 6.8%, p=0.001). An ex vivo phagocytosis assay that examined the functional effects of these polymorphisms on the defense against Mtb revealed higher phagocytosis in monocytes from males with the TLR8 -129C genotype than in those with TLR8 -129G (73.02% vs. 34.6%, p=0.03). In addition, mRNA expression and cytokine production, analyzed in the whole blood of male healthy volunteers stimulated with inactivated Mtb ex vivo, TNFα production and TLR7 expression were lower in TLR8 -129C subjects after Mtb stimulation. The ability of Mtb to survive and replicate in macrophages is crucial for chronic persistent infection. We demonstrated that PMA-stimulated THP-1 cells showed high phagocytosis of Mtb in a Mtb dose- and time-dependent manner. The phagocytosis of Mtb was markedly influenced by IFN-γ and CL075 activation, and the efficiency of Mtb phagocytosis increased to 1.53 and 1.33 folds, respectively. TLR8 was unregulated to 7.22 and 1.75 folds in response to IFN-γ and CL075 stimulation. However, after silencing TLR8 expression, the phagocytosis of Mtb was significantly decreased in PMA-stimulated THP-1 cells. In conclusion, these findings provide evidence that TLR8 genetic polymorphisms are associated with susceptibility to Mtb infection, and the link is shaped by more effective Mtb phagocytosis but impaired TLR8 signaling.
    Advisory Committee
  • Jong-Kang Liu - chair
  • Hock-Liew Eng - co-chair
  • Tsun-Mei Lin - advisor
  • Jiin-Tsuey Cheng - advisor
  • Files
  • etd-0712114-024747.pdf
  • Indicate in-campus at 3 year and off-campus access at 5 year.
    Date of Submission 2014-08-12

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