Heptose Sounds the Alarm: Innate Sensing of a Bacterial Sugar Stimulates Immunity

PAMPs Are Indicators of Microbial Identity and VirulenceThe first line of defense against infection, the innate immune system, identifies and responds to microbial threats.Central to this response is the discrimination of self from non-self.Pattern recognition receptors (PRRs) expressed by mammalian cells detect molecular signatures unique to microbes yet absent from the host.These molecules, termed pathogen-associated molecular patterns (PAMPs), are invariant structures broadly represented among microbial taxa and have essential roles in microbial physiology.Consequently, only an extremely select group of molecules have been found to function as PAMPs.It is becoming increasingly clear that rather than being redundant, PAMPs are interpreted by the innate immune system as a "pathogenic barcode" that informs the host to both the identity and infectious risk posed by a microorganism.The combination of PAMPs presented, the tissue type affected, and the subcellular compartment contaminated represent just some of the contextual signals used by the host to identify and assess the microbial threat.For example, PAMP contamination of the host cytosol is interpreted as an indicator of microbial virulence since direct cellular invasion or virulence factor-mediated translocation is a prerequisite for their presence in this normally sterile site [1].Such distinctions are critical to maintaining immune homeostasis since, despite their name, PAMPs are not unique to pathogens; instead, they can be found in virtually all microorganisms, including the commensal microflora that constitutively reside on body surfaces.