title: Absence of TRIF signaling in lipopolysaccharide-stimulated murine mast cells.
abstract: In macrophages, two signaling pathways, dependent on MyD88 or TIR domain-containing adaptor-inducing IFN-β (TRIF) signaling, emanate from the LPS receptor TLR4/MD-2. In this study, we show that in murine bone marrow-derived mast cells (BMMCs), only the MyD88-dependent pathway is activated by LPS. The TRIF signaling branch leading both to NF-κB activation and enhanced proinflammatory cytokine production, as well as to IRF3 activation and subsequent IFN-β production, is absent in LPS-stimulated BMMCs. IRF3 activation is also absent in peritoneal mast cells from LPS-injected mice. We observed strongly diminished TRAM expression in BMMCs, but overexpression of TRAM only moderately enhanced IL-6 and did not boost IFN-β responses to LPS in these cells. A combination of very low levels of TRAM and TLR4/MD-2 with the known absence of membrane-bound CD14 are expected to contribute to the defective TRIF signaling in mast cells. We also show that, unlike in macrophages, in BMMCs the TRIF-dependent and -independent IFN-αβ responses to other recognized IFN inducers (dsRNA, adenovirus, and B-DNA) are absent. These results show how the response to the same microbial ligand using the same receptor can be regulated in different cell types of the innate immune system.
authors: Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany.
authors: Simone
authors: S
authors: Keck
authors: Ines
authors: I
authors: Müller
authors: György
authors: G
authors: Fejer
authors: Iva
authors: I
authors: Savic
authors: Sandrine
authors: S
authors: Tchaptchet
authors: Peter J
authors: PJ
authors: Nielsen
authors: Chris
authors: C
authors: Galanos
authors: Michael
authors: M
authors: Huber
authors: Marina A
authors: MA
authors: Freudenberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000276:immunology*; D051218:Lymphocyte Antigen 96; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D018123:Receptors, Interleukin; D051197:Toll-Like Receptor 4; C411728:Ly96 protein, mouse; C476286:Ticam1 protein, mouse; C476416:Ticam2 protein, mouse; C493487:Tlr4 protein, mouse