Involvement of ERK, p38 and NF‐κB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells

Abstract

SUMMARYToll-like receptors (TLR) are sentinel receptors capable of recognizing pathogen-associated molecule patterns (PAMP) such as lipopolysaccharide (LPS) and CpG-containing oligonucleotides (CpG ODN). TLR2 and TLR4 are major receptors for Gram-positive and Gram-negative bacterial cell wall components, respectively. TLR9 is necessary for CpG signalling. LPS or CpG ODN can activate immature dendritic cells (DC) and induce DC maturation characterized by production of cytokines, up-regulation of co-stimulatory molecules, and increased ability to activate T cells. However, little is known regarding the regulation of TLR gene expression in mouse DC. In this study, we investigated the regulation of TLR2, TLR4 and TLR9 gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up-regulated following LPS stimulation. The up-regulation of TLR9 expression coincided with significantly increased production of tumour necrosis factor-a induced by LPS plus CpG ODN. While inhibition of extracellular signal-related kinase and NF-kB activation suppressed the up-regulation of the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS might promote the overall responses of DC to bacteria and help to explain the synergy between LPS and other bacterial products in the induction of cytokine production.

Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection

“…L. monocytogenes infection of human DC in vitro has been reported (66), but it remains to be investigated whether direct bacterial infection activates DC to become competent APC, or in fact result in dysfunction of the host cellular machinery due to overwhelming growth of intracellular bacteria. It is also known that dsRNA intermediates produced during viral replication are recognized by TLR3 (67), leading to the activation of DC and macrophages and an IFN response (68). However, infection of DC is not a prerequisite for Ag presentation since DC are known to become activated through TLR recognition of bacterial products, such as flagellin, peptidoglycan, and lipoteichoic acid from L. monocytogenes (69,70).…”

Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs

“…Different experimental conditions may account for these discrepancies, the most important being the fact that our model relies on infection with live bacteria, which implies that a much more complex process is under way and may even involve the participation of other TLRs (10).…”

“…The activation of TLRs triggers a complex series of events that culminate in enhanced transcription of proinflammatory genes, whose ultimate goal is to initiate the mechanisms that counteract infection (10). We hypothesized that I-R primes the innate immune system to overreact upon a bacterial challenge, and that this preconditioning would consist in altered levels of TLRs and proinflammatory cytokines.…”

Commensal bacteria and epithelial cross talk in the developing intestine

“…In the intestinal epithelium, DC singe stand sample antigens passing through M cells or directly from within the intestine by opening tight junctions between IECs and extending dendrites into the gut lumen [46]. Microbial stimulation through TLRs controls DC activation, maturation, and migration at least in part through NF-κB and MAPK-dependent mechanisms [47][48][49]. Intestinal DCs may retain ingested live commensal bacteria within them, migrate to the mesenteric lymph nodes, and induce secretory IgA production without systemic immune activation [50].…”