Lipoteichoic acid increases TLR and functional chemokine expression while reducing dentin formation in in vitro differentiated human odontoblasts.
Gram-positive bacteria entering the dentinal tissue during the carious process are suspected to influence the immune response in human dental pulp. Odontoblasts situated at the pulp/dentin interface are the first cells encountered by these bacteria and therefore could play a crucial role in this response. In the present study, we found that in vitro-differentiated odontoblasts constitutively expressed the pattern recognition receptor TLR1-6 and 9 genes but not TLR7, 8, and 10. Furthermore, lipoteichoic acid (LTA), a wall component of Gram-positive bacteria, triggered the activation of the odontoblasts. LTA up-regulated the expression of its own receptor TLR2, as well as the production of several chemokines. In particular, an increased amount of CCL2 and CXCL10 was detected in supernatants from LTA-stimulated odontoblasts, and those supernatants augmented the migration of immature dendritic cells in vitro compared with controls. Clinical relevance of these observations came from immunohistochemical analysis showing that CCL2 was expressed in vivo by odontoblasts and blood vessels present under active carious lesions but not in healthy dental pulps. In contrast with this inflammatory response, gene expression of major dentin matrix components (type I collagen, dentin sialophosphoprotein) and TGF-beta1 was sharply down-regulated in odontoblasts by LTA. Taken together, these data suggest that odontoblasts activated through TLR2 by Gram-positive bacteria LTA are able to initiate an innate immune response by secreting chemokines that recruit immature dendritic cells while down-regulating their specialized functions of dentin matrix synthesis and mineralization.
Laboratory Development and Regeneration of Dental Tissues, University Lyon 1, Faculty of Odontology, Institut National de la Santé et de la Recherche Médicale (INSERM) ERi76 Equipe d'Accueil 1892, Institut Fédératif de Recherche 62, Lyon, France.
Stéphanie H
SH
Durand
Vincent
V
Flacher
Annick
A
Roméas
Florence
F
Carrouel
Evelyne
E
Colomb
Claude
C
Vincent
Henry
H
Magloire
Marie-Lise
ML
Couble
Françoise
F
Bleicher
Marie-Jeanne
MJ
Staquet
Serge
S
Lebecque
Jean-Christophe
JC
Farges
D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology; D003804:Dentin / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D009804:Odontoblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009924:Organ Culture Techniques; D013682:Teichoic Acids / Q000378:metabolism / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
D018925:Chemokines; D016326:Extracellular Matrix Proteins; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid