| First Author | Lundberg AM | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 9 | Pages | 3245-52 |
| PubMed ID | 17660379 | Mgi Jnum | J:149120 |
| Mgi Id | MGI:3847628 | Doi | 10.1182/blood-2007-02-072934 |
| Citation | Lundberg AM, et al. (2007) Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. Blood 110(9):3245-52 |
| abstractText | TLR3 recognizes double-stranded RNA, a product associated with viral infections. Many details of TLR3-induced mechanisms have emerged from gene-targeted mice or inhibition studies in transformed cell lines. However, the pathways activated in human immune cells or cells from disease tissue are less well understood. We have investigated TLR3-induced mechanisms of human primary cells of the innate immune system, including dendritic cells (DCs), macrophages (MOs), endothelial cells (ECs), and synovial fibroblasts isolated from rheumatoid arthritis joint tissue (RA-SFs). Here, we report that while these cells all express TLR3, they differ substantially in their response to TLR3 stimulation. The key antiviral response chemokine IP-10 was produced by all cell types, while DCs and MOs failed to produce the proinflammatory cytokines TNFalpha and IL-6. Unexpectedly, TNFalpha was found secreted by TLR3-stimulated RA-SF. Furthermore, TLR3 stimulation did not activate NFkappaB, MAPKs, or IRF-3 in DCs and MOs, but was able to do so in ECs and RA-SF. These findings were specific for human cells, thereby revealing a complexity not previously expected. This is the first report of such cell type- and species-specific response for any TLR stimulation and helps to explain important difficulties in correlating murine models of inflammatory diseases and human inflammation. |
