CD14 is required for MyD88-independent LPS signaling.
Nat Immunol
; 6(6): 565-70, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15895089
ABSTRACT
The recessive mutation 'Heedless' (hdl) was detected in third-generation N-ethyl-N-nitrosourea-mutated mice that showed defective responses to microbial inducers. Macrophages from Heedless homozygotes signaled by the MyD88-dependent pathway in response to rough lipopolysaccharide (LPS) and lipid A, but not in response to smooth LPS. In addition, the Heedless mutation prevented TRAM-TRIF-dependent signaling in response to all LPS chemotypes. Heedless also abolished macrophage responses to vesicular stomatitis virus and substantially inhibited responses to specific ligands for the Toll-like receptor 2 (TLR2)-TLR6 heterodimer. The Heedless phenotype was positionally ascribed to a premature stop codon in Cd14. Our data suggest that the TLR4-MD-2 complex distinguishes LPS chemotypes, but CD14 nullifies this distinction. Thus, the TLR4-MD-2 complex receptor can function in two separate modes one in which full signaling occurs and one limited to MyD88-dependent signaling.
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Base de dados:
MEDLINE
Assunto principal:
Receptores Imunológicos
/
Antígenos de Diferenciação
/
Lipopolissacarídeos
/
Receptores de Lipopolissacarídeos
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article