TLR2 and TLR9 modulate enteric nervous system inflammatory responses to lipopolysaccharide
Burgueño, Juan F (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Barba, Albert (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Eyre Sánchez, Elena (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Romero Prada, Carolina (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Neunlist, Michel (INSERM, UMR913)
Fernandez, Ester (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Date:	2016
Abstract:	Accumulating evidence suggest that the enteric nervous system (ENS) plays important roles in gastrointestinal inflammatory responses, which could be in part mediated by Toll-like receptor (TLR) activation. The aim of this study was to characterise the expression and functionality of TLR2/4/9 in the ENS. TLR2/4/9 expression was assessed in the plexuses of adult rats and embryonic ENS cultures by immunofluorescence and quantitative PCR. Following stimulation with TLR2/4/9 ligands or their combinations, activation of NF-kB, production of TNF-α, IL-6 and MCP-1 and chemoattraction of RAW264. 7 macrophages were evaluated by means of Western blot, ELISA, immunofluorescence and migration assays in transwell inserts. TLR2/4/9 staining colocalised with enteric neuronal markers, whereas their presence in enteroglial processes was low to inexistent. Stimulation of ENS cultures with selective ligands induced NF-kB activation and release of cytokines and chemokines by neurons and resident immunocytes. TLR2 neutralisation before lipopolysaccharide (LPS) challenge reduced production of inflammatory mediators, whereas combination of TLR2/4 ligands promoted macrophage migration. Combined stimulation of cultures with LPS and the CpG oligonucleotide 1826 (TLR4/9 ligands) caused a synergic increase in chemoattraction and cytokine production. Our results suggest that the ENS, and particularly enteric neurons, can integrate a variety of microbial signals and respond in a relatively selective fashion, depending on the particular TLRs stimulated. These findings additionally suggest that the ENS is capable of initiating a defensive response against pathogens and expanding inflammation. The online version of this article (doi:10. 1186/s12974-016-0653-0) contains supplementary material, which is available to authorized users.
Grants:	Ministerio de Educación y Ciencia AP2005-1160 Ministerio de Educación y Ciencia AP2006-02705 Ministerio de Economía y Competitividad BFU2006-15063-C03-01 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-997
Note:	Altres ajuts: MSC/PS09/01127
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Enteric nervous system ; Enteric neuron ; TLR2 ; TLR4 ; TLR9 ; Inflammation ; Chemoattraction
Published in:	Journal of neuroinflammation, Vol. 13 (August 2016) , art.187, ISSN 1742-2094

DOI: 10.1186/s12974-016-0653-0
PMID: 27538577

15 p, 2.7 MB

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Articles > Research articles
Articles > Published articles