Expression level of human TLR4 rather than sequence is the key determinant of LPS responsiveness

PLoS One. 2017 Oct 11;12(10):e0186308. doi: 10.1371/journal.pone.0186308. eCollection 2017.

Abstract

To address the role of Toll-like receptor 4 (TLR4) single nucleotide polymorphisms (SNP) in lipopolysaccharide (LPS) recognition, we generated mice that differed only in the sequence of TLR4. We used a bacterial artificial chromosome (BAC) transgenic approach and TLR4/MD-2 knockout mice to specifically examine the role of human TLR4 variants in recognition of LPS. Using in vitro and in vivo assays we found that the expression level rather than the sequence of TLR4 played a larger role in recognition of LPS, especially hypoacylated LPS.

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • Cytokines / blood
  • Escherichia coli / chemistry
  • Gene Dosage
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Mutant Proteins / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Pseudomonas aeruginosa / chemistry
  • Spleen / cytology
  • Staining and Labeling
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Cytokines
  • Lipopolysaccharides
  • Mutant Proteins
  • TLR4 protein, human
  • Toll-Like Receptor 4