Intracellular sensors of extracellular bacteria

Initial recognition of bacteria by the innate immune system is thought to occur primarily by germline-encoded pattern recognition receptors (PRRs). These receptors are present in multiple compartments of host cells and are thus capable of surveying both the intracellular and extracellular milieu for bacteria. It has generally been presumed that the cellular location of these receptors dictates what type of bacteria they respond to: extracellular bacteria being recognized by cell surface receptors, such as certain Toll-like receptors, and bacteria that are capable of breaching the plasma membrane and entering the cytoplasm, being sensed by cytoplasmic receptors, including the Nod-like receptors (NLRs). Increasingly, it is becoming apparent that this is a false dichotomy and that extracellular bacteria can be sensed by cytoplasmic PRRs and this is crucial for controlling the levels of these bacteria. In this review, we discuss the role of two NLRs, Nod1 and Nod2, in the recognition of and response to extracellular bacteria.