Recognition Of Pathogens By Pattern Recognition Receptors

Macrophages represent the cornerstone of the innate immune response to infection. They must be able to specifically define the threat and then formulate an appropriate, and measured, response. This requirement is not trivial; antigen recognition in the adaptive immune response is exquisitely tailored by mechanisms involving gene rearrangement and affinity maturation. How then can a macrophage, with only germ line receptors, precisely gauge the nature of the threat? The answer lies largely in pattern recognition receptors. The term "pattern recognition receptor" (PRR) was suggested by Janeway to describe a generic class of molecules that recognise structural features found on pathogens, but not the host. As the pattern recognition receptors are invariant molecules, this implies that the pathogen-derived components are necessary for the survival of the microbe, and thus cannot be mutated [4]. These structural features have been referred to as pathogen-associated molecular patterns, or PAMPS. However, it should be noted that these structures are also found on a variety of microbes that are not pathogenic, like the commensals inhabiting our intestines. In bacteria, the vast majority of PAMPS are associated with the cell wall (Fig. 1). These include the lipopolysaccharides (LPS) of Gram-negative bacteria and the lipoteichoic acids (LTA) of Gram-positive bacteria. However, host cells also recognise microbial molecules other than cell wall components. For example, the unmethylated CpG dinucleotide motif of bacterial DNA has immunostimulatory properties [5], as does flagellin, a protein component of the motile machinery of bacteria [6]. Other pathogens including viruses, fungi, and protozoan parasites also have immunostimulatory structures. These include different proteins, double-stranded RNA of viruses [7], and glycosyl-phosphatidyl inositol (GPI) anchors of protozoa [8].

PRRs can be membrane bound or soluble proteins. In some invertebrate species like the fruit lili WW mVW

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