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Peptidoglycan Signaling in Innate Immunity and Inflammatory Disease*

C. McDonald,N. Inohara,G. Núñez

Published 2005 in Journal of Biological Chemistry

ABSTRACT

The ability to detect harmful pathogens and eradicate them is essential for the survival of an organism. One of the first lines of defense is the innate immune system, a broad specificity inflammatory response characterized by the recruitment and activation of phagocytes. This type of immune response is well conserved from invertebrates through higher mammals and is stimulated by the recognition of conserved components of microorganisms called pathogen-associated molecular patterns (PAMPs).1 These PAMPs consist of molecules not found in the host, including bacterial cell wall components such as peptidoglycan (PGN). Recognition of PAMPs by specific proteins called pattern recognition molecules (PRMs) activates inflammatory signaling pathways and the stimulation of an immune response. Recent studies challenging the role of Toll-like receptor 2 (TLR2) as the major PGN receptor, the genetic dissection of the role of mammalian peptidoglycan response proteins (PGRPs) in immune responses, and the identification of Nodi, Nod2, and cryopyrin as PGN response proteins have put the spotlight on the mechanisms of PGN recognition and signaling in innate immunity. In addition, mutations found in Nod2 and cryopyrin are genetically associated with the development of specific inflammatory diseases. This review will focus on recent findings about the proteins involved in binding to and stimulating an intracellular signaling response to PGN and their relationship to inflammatory disease.

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