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The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors
- Source :
- Nature immunology. 8(6)
- Publication Year :
- 2007
-
Abstract
- Immunoreceptor tyrosine-based activation motifs (ITAMs) are crucial in antigen receptor signaling in acquired immunity. Although receptors associated with the ITAM-bearing adaptors FcRgamma and DAP12 on myeloid cells have been suggested to activate innate immune responses, the mechanism coupling those receptors to 'downstream' signaling events is unclear. The CARMA1-Bcl-10-MALT1 complex is critical for the activation of transcription factor NF-kappaB in lymphocytes but has an unclear function in myeloid cells. Here we report that deletion of the gene encoding the Bcl-10 adaptor-binding partner CARD9 resulted in impaired myeloid cell activation of NF-kappaB signaling by several ITAM-associated receptors. Moreover, CARD9 was required for Toll-like receptor-induced activation of dendritic cells through the activation of mitogen-activated protein kinases. Although Bcl10-/- and Card9-/- mice had similar signaling impairment in myeloid cells, Card11-/- (CARMA1-deficient) myeloid cell responses were normal, and although Card11-/- lymphocytes were defective in antigen receptor-mediated activation, Card9-/- lymphocytes were not. Thus, the activation of lymphoid and myeloid cells through ITAM-associated receptors or Toll-like receptors is regulated by CARMA1-Bcl-10 and CARD9-Bcl-10, respectively.
- Subjects :
- T-Lymphocytes
Immunology
CD33
Amino Acid Motifs
Nerve Tissue Proteins
Biology
Lymphocyte Activation
Mice
hemic and lymphatic diseases
Immunology and Allergy
Animals
Lectins, C-Type
Listeriosis
Myeloid Cells
Receptor
Adaptor Proteins, Signal Transducing
B-Lymphocytes
Toll-Like Receptors
NF-kappa B
Signal transducing adaptor protein
Membrane Proteins
Cell Differentiation
Dendritic Cells
Cell biology
CARD Signaling Adaptor Proteins
Enzyme Activation
Guanylate Cyclase
Toll
Myeloid cells
Myeloid Differentiation Factor 88
Cancer research
biology.protein
Tyrosine
Mitogen-Activated Protein Kinases
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 15292908
- Volume :
- 8
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature immunology
- Accession number :
- edsair.doi.dedup.....d6537b0312f6a4b126b16c590c3bc96e