Disease relevance of TLR4

• Their coordinated regulation explains our unexpected observation that pure Staphylococcus aureus infections caused a strong increase also in TLR4 mRNA abundance [1].
• Immune cells detect E. coli by Toll-like receptor 4 (TLR4) binding its pathogenic ligand, lipopolysaccharide (LPS), although signaling requires accessory molecules such as CD14 [2].
• Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus [3].
• BACKGROUND: During systemic gram-negative bacterial infections, lipopolysaccharide (LPS) ligation to the hepatic Toll-like receptor-4 complex induces the production of hepatic acute phase proteins that are involved in the host response to infection and limit the associated inflammatory process [4].
• We show here that live Gram-negative bacteria can similarly stimulate this pathway, resulting in upregulation of the beta-defensin tracheal antimicrobial peptide (TAP) in primary cultures of bovine tracheal epithelial cells (TECs), by a Toll-like receptor 4 (TLR4)-mediated pathway [5].

High impact information on TLR4

• Haplotype variation in bovine Toll-like receptor 4 and computational prediction of a positively selected ligand-binding domain [6].
• In vivo, MMTV increased the number of dendritic cells in neonatal Peyer's patches and their expression of CD71; both these effects were dependent on TLR4 [3].
• Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus [2].
• Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways [7].
• In the present study, we have asked whether bovine LF (bLF)-induced macrophage activation is TLR4-dependent [7].

Biological context of TLR4

• Preinfection of bovine MPhi by BVDV resulted in upregulation of TLR2- and TLR4-mediated NO synthesis [8].

Anatomical context of TLR4

• The number of TLR2 copies correlated well with those of TLR4, indicating coordinated regulation of these two PRRs during infection of the udder [1].
• For the first time, Toll-like receptor 4 mRNA and CD14 mRNA and protein were detected in bovine endometrial stromal and epithelial cells by RT-PCR and flow cytometry [2].
• However, in macrophages from congenic TLR4(-/-) C.C3-Tlr4(lps-d) mice, CD40 was not expressed while IL-6 secretion was increased relative to wild-type cells [7].

Associations of TLR4 with chemical compounds

• Mammalian cells respond to bacterial lipopolysaccharide (LPS) through a cognate receptor: Toll-like receptor 4 (TLR4) [9].

Analytical, diagnostic and therapeutic context of TLR4

• The effect was also abrogated in either C3H/HeJ mouse-derived CD19(+) cell culture or the anti-TLR4 antibody-added culture [10].

References