1. SLAMF1 is required for TLR4-mediated TRAM-TRIF dependent signaling in human macrophages
- Author
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Ninghai Wang, Terje Espevik, Astrid Skjesol, Harald Husebye, Gabriel Mary Richard, Richard Kumaran Kandasamy, Mariya Yurchenko, Liv Ryan, and Cox Terhorst
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,THP-1 Cells ,Endocytic recycling ,Endosomes ,Biology ,Protein Serine-Threonine Kinases ,Article ,03 medical and health sciences ,0302 clinical medicine ,Signaling Lymphocytic Activation Molecule Family Member 1 ,Phagosomes ,Escherichia coli ,Animals ,Humans ,Protein Interaction Domains and Motifs ,Receptor ,Research Articles ,Phagosome ,Adaptor Proteins, Signal Transducing ,Mice, Knockout ,Macrophages ,HEK 293 cells ,Signal transducing adaptor protein ,Cell Biology ,Interferon-beta ,Macrophage Activation ,Cell biology ,Mice, Inbred C57BL ,Toll-Like Receptor 4 ,Adaptor Proteins, Vesicular Transport ,Protein Transport ,030104 developmental biology ,HEK293 Cells ,TRIF ,rab GTP-Binding Proteins ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,TLR4 ,Interferon Regulatory Factor-3 ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
Yurchenko et al. discover that the Ig-like receptor molecule SLAMF1 enhances production of type I interferon induced by Gram-negative bacteria through modulation of MyD88-independent TLR4 signaling. This makes SLAMF1 a potential target for controlling inflammatory responses against Gram-negative bacteria., Signaling lymphocytic activation molecule family 1 (SLAMF1) is an Ig-like receptor and a costimulatory molecule that initiates signal transduction networks in a variety of immune cells. In this study, we report that SLAMF1 is required for Toll-like receptor 4 (TLR4)-mediated induction of interferon β (IFNβ) and for killing of Gram-negative bacteria by human macrophages. We found that SLAMF1 controls trafficking of the Toll receptor–associated molecule (TRAM) from the endocytic recycling compartment (ERC) to Escherichia coli phagosomes. In resting macrophages, SLAMF1 is localized to ERC, but upon addition of E. coli, it is trafficked together with TRAM from ERC to E. coli phagosomes in a Rab11-dependent manner. We found that endogenous SLAMF1 protein interacted with TRAM and defined key interaction domains as amino acids 68 to 95 of TRAM as well as 15 C-terminal amino acids of SLAMF1. Interestingly, the SLAMF1–TRAM interaction was observed for human but not mouse proteins. Overall, our observations suggest that SLAMF1 is a new target for modulation of TLR4–TRAM–TRIF inflammatory signaling in human cells., Graphical Abstract
- Published
- 2018