Toll-like receptor (TLR)2 and TLR3 synergy and cross-inhibition in murine myeloid dendritic cells.
Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs) and in the induction of immune responses. Few studies have been devoted to address the impact of TLR2 (a fully MyD88-dependent receptor) and TLR3 (a fully TRIF-dependent receptor) co-activation on DC functions, especially in the mouse system. Using canonical agonists, we show that TLR2 acts in concert with TLR3 to induce the synthesis of inflammatory cytokines (TNF-alpha, IL-6), of some IL-12 family members (IL-12p40, IL-12p23, IL-27p28) and of the Notch ligand Delta-4 by mouse DCs. In contrast, TLR2 interferes with the TLR3-induced expression of type I interferon stimulated genes (MIG/CXCL9, IP-10/CXCL10, GARG39) and IL-12p35. We also report that TLR2 cooperates with TLR3 to enhance the DC-mediated production of IFN-gamma by Natural Killer cells and by conventional Ag-specific T lymphocytes. To conclude, our data support the existence of TLR2 and TLR3 synergy and cross-inhibition in DCs that could be important to strengthen immune responses during infection.
Vanhoutte
François
F
Institut National de la Recherche Médicale, U547, Lille F-59019, France.
Paget
Christophe
C
Breuilh
Laetitia
L
Fontaine
Josette
J
Vendeville
Catherine
C
Goriely
Stanislas
S
Ryffel
Bernhard
B
Faveeuw
Chistelle
C
Trottein
François
F
D000818:Animals; D000943:Antigens, Differentiation; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D007111:Immunity, Cellular; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020239:Receptor Cross-Talk; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
D000943:Antigens, Differentiation; D000939:Epitopes; D018836:Inflammation Mediators; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D018664:Interleukin-12; D007371:Interferon-gamma