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

Abstract

S U M M A R Y The aim of the present study was to evaluate the expression of innate immunity receptors belonging to the Toll-like family in the neural plexuses of the different tracts of murine intestine, of the human ileum, and in lower dorsal root ganglia (DRGs) from where extrinsic afferents to these plexuses originate. Results obtained by immunohistochemistry and immunofluorescence on paraffin-embedded tissue and whole-mount preparations show that Toll-like receptors (TLRs) -3 and -7, recognizing viral RNA, and TLR4, recognizing lipopolysaccharide (membrane component of Gram-negative bacteria), are expressed in the myenteric and submucous plexuses of murine intestine and human ileum, and in DRGs primary sensory neurons. They also show that TLR4 immunostaining is stronger in murine distal large bowel. In murine tissue, expression of TLRs was present in both neurons and glial cells. These observations indicate that the enteric neural network might be directly activated by bacterial and viral components and is therefore more in the forefront than previously envisaged in defense responses of the intestinal wall and in the cross-talk with intestinal microbiota. They also highlight the presence of a peripheral neural network that by way of hardwired neurotransmission could potentially convey to the central nervous system specific information on our microbial counterpart and invading or potentially invading pathogens. (J Histochem Cytochem

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

“…40 For example, LPS can activate Toll-Like receptors that are present on epithelial cells, enteric neurons, sensory afferent neurons in the spine, and various cells in the brain, modulating their activity and affecting the function of both ENS and CNS. [41][42][43][44] As mentioned above, the interaction between the gut and brain is bidirectional-the CNS can affect gut permeability and increased gut permeability in turn can alter CNS function. In both animal models of stress and human subjects who were exposed to stress, the intestinal barrier is impaired.…”

Prostaglandine D2 et homéostasie de la barrière épithéliale intestinale

“…Initialement considéré comme une cible de l'inflammation, du fait de l'observation de nombreuses lésions et modifications morphologiques, neurochimiques et fonctionnelles [40], le système nerveux entérique apparaît aujourd'hui comme un acteur essentiel du processus inflammatoire. En effet, les cellules gliales entériques expriment la machinerie cellulaire nécessaire à l'intégra-tion d'un signal inflammatoire ayant pour origine les Toll-like receptors [41]. En réponse à ce signal, elles sont capables de proliférer et de sécréter des cytokines pro-inflammatoires comme l'IL-6 ou l'IL-1 [36,42], ou encore des prostanoïdes issus de la voie métabolique COX-LPGDS [15,43].…”

26 Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High Fat Diet Fed Mice

“…21,22 The endotoxemia associated with a high-fat diet could initiate myenteric inducible NOS activation, known to increase in neurons after the systemic administration of LPS, 56 and can induce an overproduction of NO in nitrergic neurons, leading to oxidative stress and apoptosis. 42,57 This will be the focus of our future studies as we continue to understand the mechanisms of a HFDinduced nitrergic enteric neuronal degeneration and delayed colonic transit.…”