Aug. 14, 2009 Edith Hessel and colleagues, at Dynavax
Technologies Corporation, Berkeley, have identified the reason
that humans and rodents respond differently to a molecule that
is being developed to treat allergic diseases. Molecules that
trigger the protein TLR9 are being developed as a potential
therapeutic for allergic diseases. While they have been shown to
be safe and well-tolerated when inhaled by people, they cause
severe lung inflammation and toxicity when inhaled by rodents.
In the study, the toxicity of one of the molecules under
development was found to depend on TLR9 and the soluble immune
molecule TNF-alpha in mice. Importantly, TLR9 is expressed on
many immune cell types in the mouse (monocyte/macrophage cells,
B cells, and pDCs) and only on B cells and pDCs in humans. The
toxicity in mice was found to be independent of B cells and
pDCs, meaning that other immune cells expressing TLR9 were
responsible for TNF-alpha production. As human TLR9-expressing
cells did not produce TNF-alpha in respon