Genetic Modulation of TLR8 Response following Bacterial Phagocytosis
Michael P Gantier, Aaron T Irving, Maria Kaparakis-Liaskos, Dakang Xu, Vanessa A Evans, Paul U Cameron, James A Bourne, Richard L Ferrero, Matthias John, Mark A Behlke, Bryan RG Williams
Human Mutation | WILEY | Published : 2010
Human Toll-like receptors (TLRs) TLR7, TLR8, and TLR9 are important immune sensors of foreign nucleic acids encountered by phagocytes. Although there is growing evidence implicating TLR7 and TLR9 in the detection of intracellular pathogenic bacteria, characterization of such a role for TLR8 is currently lacking. A recent genetic study has correlated the presence of a TLR8 single nucleotide polymorphism (SNP) (rs3764880:A>G; p.Met1Val) with the development of active tuberculosis, suggesting a role for TLR8 in the detection of phagosomal bacteria. Here we provide the first direct evidence that TLR8 sensing is activated in human monocytic cells following Helicobacter pylori phagocytosis. In add..View full abstract
Awarded by Australian National Health and Medical Research Council
We are grateful to M. Seeger for his assistance in the cloning of the 5'UTR TLR8 reporters and to Claire E. McCoy for her advice in the revision of this manuscript. This work was supported by the Australian National Health and Medical Research Council (Project Grant number 491106 [B.R.G.W.] and 3203656 [R.L.F]; and Program Grant number 358399 [P.U.C., V.E.]), and the Victorian Government's Operational Infrastructure Support Program. R.L.F. is an NHMRC Senior Research Fellow.