| First Author | Jiang Z | Year | 2005 |
| Journal | Nat Immunol | Volume | 6 |
| Issue | 6 | Pages | 565-70 |
| PubMed ID | 15895089 | Mgi Jnum | J:98908 |
| Mgi Id | MGI:3580723 | Doi | 10.1038/ni1207 |
| Citation | Jiang Z, et al. (2005) CD14 is required for MyD88-independent LPS signaling. Nat Immunol 6(6):565-70 |
| abstractText | 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. |
