Activation of smooth muscle and myenteric plexus cells of jejunum via toll‐like receptor 4

Abstract

The cell types of the gut expressing Toll-like receptor 4, which recognizes specifically bacterial lipopolysaccharides, as well as the functionality of this receptor, have remained controversial. We aimed to clarify these issues. Mouse and human intestinal specimens were stained immunohistochemically to detect Toll-like receptor 4 expression. Smooth muscle and myenteric plexus cells but not enterocytes revealed receptor expression. Murine intestinal smooth muscle and myenteric plexus cells but not enterocytes showed nuclear translocation of nuclear factor-kappaB after in vivo stimulation with lipopolysaccharide. Moreover, lipopolysaccharide added to human jejunum biopsies free of epithelial cells induced release of interleukin-8 (IL-8). We can conclude that Toll-like receptor 4 is not expressed in epithelial layer, but rather on smooth muscle and myenteric plexus cells and that expression is functional. The expression of Toll-like receptor 4 on smooth muscle and myenteric plexus cells is consistent with the possibility that these cells are involved in intestinal immune defense; the low or absent expression of Toll-like receptor 4 on enterocytes might explain the intestinal epithelium hyporesponsiveness to the abundance of LPS in the intestinal lumen.

Toll-like Receptors 3, 4, and 7 Are Expressed in the Enteric Nervous System and Dorsal Root Ganglia

“…We also show that TLR4, besides being expressed in the neurons of the myenteric plexus of the murine jejunum (Rumio et al 2006), is also expressed in the remaining intestine and in the submucous plexus, in both neurons and glial cells, and that the intensity of its immunolabeling is stronger in the distal large bowel. Furthermore, we report the expression of the three receptors in lower thoracic and lumbosacral murine DRGs.…”

“…They can be subdivided into several subfamilies that recognize related MAMPs belonging to bacteria, fungi, parasites, viruses, and hosts (Akira et al 2006). TLR activation by pathogens triggers rapid and localized responses mediated by phagocytes through different signaling pathways, leading to the production of proinflammatory cytokines, chemokines, and type 1 interferon (Akira et al 2006).…”

Role of Toll-like receptors in gastrointestinal malignancies

“…*Protein expression has been confirmed (Rock et al, 1998;Cario and Podolsky, 2000;Furrie et al, 2005;Schmausser et al, 2005). In addition to IEC, lamina propria macrophages express TLR4 and TLR2 (Hausmann et al, 2002), and jejunal smooth muscle cells and myenteric prexus express TLR4 (Rumio et al, 2006). a Denotes that the receptor has been shown to be functional in response to the appropriate ligand (Naik et al, 2001).…”

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

“…Remarkably, oral treatment of these offspring with the comThe TLRs are an important subgroup of PRRs that play a key role in the maintenance of symbiosis between gut microbiota and the host (94,106). Recent expression analysis indicated that TLR3 and TLR7, which recognize viral RNA, and TLR4, which recognizes LPS, a major component of gram-negative bacteria, are expressed by enteric neurons and glia, suggesting that ENS lineages have the potential to respond directly to stimuli derived from the microbial flora (107)(108)(109). In support of this idea, in vitro studies with isolated rat myenteric plexus demonstrated a direct effect of LPS on EGCs, indicated by the increased production of the pro-inflammatory factors IL-1 and prostaglandin E2 and the consequent potentiation of bradykinin-induced intracellular Ca 2+ flux in neurons (110).…”