Within a few years of the discovery of Toll-like receptors (TLRs) and their role in innate immunity, viral and bacterial proteins were recognized to antagonize TLR signal transduction. Since then, as TLR signaling networks were unraveled, microbial systems have been discovered that target nearly every component within these pathways. However, recent findings as well as some notable exceptions promote the idea that more of these systems have yet to be discovered. For example, we know very little about microbial systems for directly targeting non-cytoplasmic portions of TLR signaling pathways, that is, the ligand interacting portions of the receptor itself. In this review, we compare and contrast strategies by which bacteria and viruses antagonize TLR signaling networks to identify potential areas for future research.
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