Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems.
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 w...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1797100808675786752 |
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| author | Lundberg, A Drexler, S Monaco, C Williams, L Sacre, S Feldmann, M Foxwell, B |
| author_facet | Lundberg, A Drexler, S Monaco, C Williams, L Sacre, S Feldmann, M Foxwell, B |
| author_sort | Lundberg, A |
| collection | OXFORD |
| description | 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 (MØs), 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 MØs 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 MØs, 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. |
| first_indexed | 2024-03-07T05:42:53Z |
| format | Journal article |
| id | oxford-uuid:e63128c2-b728-4a67-99e0-c26f22f7aef2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:42:53Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:e63128c2-b728-4a67-99e0-c26f22f7aef22022-03-27T10:29:23ZKey differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e63128c2-b728-4a67-99e0-c26f22f7aef2EnglishSymplectic Elements at Oxford2007Lundberg, ADrexler, SMonaco, CWilliams, LSacre, SFeldmann, MFoxwell, BTLR3 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 (MØs), 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 MØs 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 MØs, 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. |
| spellingShingle | Lundberg, A Drexler, S Monaco, C Williams, L Sacre, S Feldmann, M Foxwell, B Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. |
| title | Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. |
| title_full | Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. |
| title_fullStr | Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. |
| title_full_unstemmed | Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. |
| title_short | Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. |
| title_sort | key differences in tlr3 poly i c signaling and cytokine induction by human primary cells a phenomenon absent from murine cell systems |
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