In addition to the TLRs, NLRs are critically involved in the sensing of bacterial pathogens. NOD1 senses diaminopimelic acid-containing peptidoglycan present in Gram-negative bacteria, whereas NOD2 senses the muramyl dipeptide present in most organisms. Because of the apparent lack of direct effects on cell signaling induced by activators of NLRs, it is suggested that their role in pathogen sensing is one of cooperation with the TLRs (107) . However, studies suggested that the actions of NOD1 vary between cell types and, unlike those seen with LPS, the in vivo effects may be independent of leukocyte activation. For instance, Cartwright and colleagues have shown that although selective activation of NOD1 in macrophages has no apparent effect, in vascular cells NOD1 activation results in the profound induction of NOSII and shock in vivo (108) .