Nod-like receptors: sentinels at host membranes.

Innate immune detection of danger signals and microbial motifs is achieved by distinct families of pattern recognition molecules. These include the membrane-anchored Toll-like receptors (TLRs), as well as cytosolic Nod-like receptors (NLRs) and Rig-I-like receptors (RLRs). The precise mode of NLR activation in the host cytosol remains poorly defined, as evidence of direct interaction between NLRs and danger- or microbial-associated molecular patterns remains elusive. However, a number of convergent observations now suggest that activation of some NLRs occurs at the level of host membranes or as a consequence of membrane damage. This review focuses on this emerging theme and discusses the functional consequences of innate immune sensing at the vicinity of the membrane. Copyright 2010 Elsevier Ltd. All rights reserved.