Microbial TIR domains: not necessarily agents of subversion?

The Toll/interleukin-1 receptor (TIR) domain plays a crucial role in the mammalian innate immune response. Recently, proteins containing TIR domains have been described in bacteria and it has been suggested that these bacterial proteins are involved in subversion of the vertebrate immune system. Here we describe the distribution of TIR-domain proteins among bacteria, fungi, archaea and viruses and evaluate the subversion hypothesis in the light of our findings. We suggest that most TIR domains in bacteria have nothing to do with subverting eukaryotic cells; instead, TIR domains function simply as general purpose protein-protein interaction domains put to diverse uses.