Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response.
Activation of dendritic cells (DC) by microbial products via Toll-like receptors (TLR) is instrumental in the induction of immunity. In particular, TLR signaling plays a major role in the instruction of Th1 responses. The development of Th2 responses has been proposed to be independent of the adapter molecule myeloid differentiation factor 88 (MyD88) involved in signal transduction by TLRs. In this study we show that flagellin, the bacterial stimulus for TLR5, drives MyD88-dependent Th2-type immunity in mice. Flagellin promotes the secretion of IL-4 and IL-13 by Ag-specific CD4(+) T cells as well as IgG1 responses. The Th2-biased responses are associated with the maturation of DCs, which are shown to express TLR5. Flagellin-mediated DC activation requires MyD88 and induces NF-kappaB-dependent transcription and the production of low levels of proinflammatory cytokines. In addition, the flagellin-specific response is characterized by the lack of secretion of the Th1-promoting cytokine IL-12 p70. In conclusion, this study suggests that flagellin and, more generally, TLR ligands can control Th2 responses in a MyD88-dependent manner.
Didierlaurent
Arnaud
A
Swiss Institute for Experimental Cancer Research and Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Ferrero
Isabel
I
Otten
Luc A
LA
Dubois
Bertrand
B
Reinhardt
Monique
M
Carlsen
Harald
H
Blomhoff
Rune
R
Akira
Shikuo
S
Kraehenbuhl
Jean-Pierre
JP
Sirard
Jean-Claude
JC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000502:physiology; D005408:Flagellin / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D053594:Myeloid Differentiation Factor 88; D010047:Ovalbumin / Q000276:immunology; D021122:Protein Subunits / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology*; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D021122:Protein Subunits; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin