Whereas detection of extracellular LPS and ensuing immune responses through TLR4 signaling pathway plays a major role in the primary detection of LPS, the recognition of cytosolic LPS by intracellular proteases caspase-4/5 (and their mouse homologue caspase-11) is important at a later stage of severe bacterial infection (28–31). This evidence concerns the gene TLR4 and bacterial infectious disease.