Intracellular vs extracellular recognition of pathogens--common concepts in mammals and flies.

There are common themes in innate immune defense systems across the animal and plant kingdoms. Pathogen recognition is commonly based on the identification of microbial molecular patterns by defined receptors and the subsequent activation of signaling pathways that initiate a defense response to fend off the invading microorganism. The existence of mammalian Toll-like receptors (TLRs) and the recent identification of two mammalian nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins (NOD1 and NOD2) as intracellular sensors of bacterial products bring new insights into the possibility of extracellular versus intracellular pathogen recognition and signal transduction depending on the nature of the infection. The homology between TLRs and the Toll system in Drosophila suggests that conserved defense mechanisms are likely to be shared by diverse organisms.