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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3245-3252. Prepublished online as a Blood First Edition Paper on July 27, 2007; DOI 10.1182/blood-2007-02-072934.
IMMUNOBIOLOGY Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems1 Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology, and Medicine, London, United Kingdom
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 TNF
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
and IL-6. Unexpectedly, TNF
B, 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. 
