Differential induction of Toll-like receptor gene expression in equine monocytes activated by Toll-like receptor ligands or TNF-α

Abstract

Toll-like receptors (TLRs) function as sentinels for the innate immune system, detecting microbial ligands during infection and inflammation. Previous studies indicate that activation of these receptors on equine monocytes leads to discrete pro- and anti-inflammatory responses that are mediated through the induction of specific cytokine genes. However, less is known regarding the regulation of TLR gene expression in these cells. Therefore, we investigated the effects of ligands recognized by TLR2, 3 or 4 upon TLR2, 3 and 4 gene expression by equine monocytes. We determined that incubation of monocytes with TLR2 and 4 ligands, which signal through the intracellular adaptor protein MyD88, induces expression of the TLR2 and 4 genes, but not the TLR3 gene. Conversely, incubation with a TLR3 ligand, which recruits the TRIF adaptor protein, selectively induces expression of the TLR3 gene, but not TLR2 or 4 genes. Furthermore, incubation of these cells with TNF-α, the pro-inflammatory cytokine that is a hallmark of TLR activation, does not affect expression of the three TLR genes. These findings suggest that exposure of equine monocytes to microbial ligands but not to endogenous inflammatory mediators may initiate responses that alter the horse's sensitivity to other microbial components during infections.