Interplay of protease-activated receptors and NOD pattern recognition receptors in epithelial innate immune responses to bacteria.
Protease-activated receptors (PARs), nucleotide-binding oligomerization domain (NOD) receptors and Toll-like receptors (TLRs) play a role in innate immunity, but little is known about interaction between these receptors. The goal of this study was to investigate how silencing one receptor affects the expression of other receptors and downstream innate immune markers in response to bacteria. Human gingival epithelial cells (GECs) were transfected with siRNA specific for PAR1 or PAR2, then stimulated with periopathogen Porphyromonas gingivalis, bridging organism between pathogens and non-pathogens Fusobacterium nucleatum, or non-pathogen Streptococcus gordonii. PAR1 or PAR2 knock-down resulted in up-regulated NOD1 and NOD2 expression with P. gingivalis or F. nucleatum stimulation (p<0.01), as well as enhanced TLR2 and TLR4 expression when cells were stimulated by bacteria that utilize TLR2 or TLR4, respectively. Involvement of PARs for induction of CC chemokine ligand 20 (CCL20), a cytokine with antimicrobial properties, was observed following stimulation of the three bacterial species. Furthermore, results from multiple cytokine ELISA array showed receptors utilized in the induction of various innate immune markers are tailored to individual bacterium tested. Our data suggest complex interplay of several receptors is required for appropriate innate immune responses to the different types of bacteria present within the oral cavity and that receptor expression itself is altered depending on which organism the cell encounters.
Chung
Whasun O
WO
Department of Oral Biology, University of Washington, Seattle, WA 98195-7132, USA.
An
Jonathan Y
JY
Yin
Lei
L
Hacker
Beth M
BM
Rohani
Maryam G
MG
Dommisch
Henrik
H
DiJulio
Dennis H
DH
D016866:Bacteroidaceae Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005674:Fusobacterium Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016967:Fusobacterium nucleatum / Q000276:immunology*; D005881:Gingiva / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D053474:Nod1 Signaling Adaptor Protein / Q000096:biosynthesis / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity; D034741:RNA, Small Interfering / Q000235:genetics; D020239:Receptor Cross-Talk; D044463:Receptor, PAR-1 / Q000235:genetics; D044464:Receptor, PAR-2 / Q000235:genetics; D013290:Streptococcal Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054773:Streptococcus gordonii / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics
D054418:Chemokine CCL20; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4