Pathogen Recognition

The inherent capability of the innate immune system to respond to a vast number of pathogens is mediated by its ability to recognize highly conserved motifs shared by diverse pathogens.[1-3] Examples of these motifs commonly referred to as pathogen-associated molecular patterns (PAMPs) include the bacterial cell wall components, lipopolysaccharide (LPS), peptidoglycan (PGN), and lipoteichoic acid (LTA), as well as unmethylated cytosine phosphate guanine (CpG) residues present in the DNA of lower microorganisms.[2] Because these PAMPs are commonly expressed by pathogenic organisms, but not by the host, the innate immune system is capable of differentiating self from nonself. Further, the ability to recognize common PAMPs on distinct pathogens enables the innate immune system to respond to vast numbers of infectious agents with only a limited repertoire of host recognition elements.

Innate recognition of PAMPs is mediated by evolu-tionarily conserved pattern recognition receptors (PRRs) and molecules (PRMs) expressed by a variety of cell types, including endothelial and epithelial cells, neutro-phils, and cells of monocytic lineage.[1-3] The specificity of a given PRR is identical among all cells of one type (e.g., macrophages) that display that given PRR.[1] Toll-like receptors (TLRs) comprise a family of PRRs that are capable of recognizing distinct PAMPs. At least 10 members of the TLR family have been identified in mammals.[4] Each member is capable of recognizing a distinct PAMP. For example, TLR-2 and TLR-4 recognize the bacterial cell wall constituents LTA and LPS, respectively.

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