Toll-like Receptor 4 is an evolutionarily conserved microbe associated molecular pattern receptor well known for its sensitivity to bacterial lipopolysaccharides (LPS). LPS is a major cell wall component in all Gram-negative bacteria and a potent activator of the innate immune response in mammals.
Chicken TLR4 encodes a 843-amino-acid protein that shows 46% identity to human TLR4. Like its human homologue chicken TLR4 contains a leucine-rich repeat extracellular domain, a short transmembrane domain typical of type I transmembrane proteins, and a Toll-interleukin-1R signaling domain.(Lebeque et al. 2003). Chicken TLR4 was shown to sense LPS of diverse Gram-negative bacteria (Kogut et al. 2005, Leveque et al. 2003). The major difference between mammalian and chicken TLR signaling is the lack of MyD88-independent IFN-beta production in chicken after TLR4 activation (Keestra et al. 2008, Zoete et al. 2009). Unlike its human counterpart activated chicken TLR4 exclusively induces the MyD88/TIRAP-dependent, but not the TRAM/TRIF mediated signaling pathway. At present, inspection of the chicken genome indicated no orthologs for intracellular human adaptor TRAM (Keestra et al. 2008), which acts as a bridge to recruit TRIF to activated TLR4.