| First Author | Keck S | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 9 | Pages | 5478-88 |
| PubMed ID | 21441453 | Mgi Jnum | J:173118 |
| Mgi Id | MGI:5009751 | Doi | 10.4049/jimmunol.1000458 |
| Citation | Keck S, et al. (2011) Absence of TRIF signaling in lipopolysaccharide-stimulated murine mast cells. J Immunol 186(9):5478-88 |
| abstractText | In macrophages, two signaling pathways, dependent on MyD88 or TIR domain-containing adaptor-inducing IFN-beta (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-kappaB activation and enhanced proinflammatory cytokine production, as well as to IRF3 activation and subsequent IFN-beta 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-beta 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-alphabeta 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. |
