Absence of TRIF signaling in lipopolysaccharide-stimulated murine mast cells.
J Immunol
; 186(9): 5478-88, 2011 May 01.
Article
em En
| MEDLINE
| ID: mdl-21441453
ABSTRACT
In macrophages, two signaling pathways, dependent on MyD88 or TIR domain-containing adaptor-inducing IFN-ß (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-ß 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-ß 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-αß 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Lipopolissacarídeos
/
Proteínas Adaptadoras de Transporte Vesicular
/
Mastócitos
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article