The role of NOD-like Receptors in shaping adaptive immunity

Abstract

Not only does the innate immune system represent the first line of defense against invading pathogens, but it is also responsible for instructing appropriate adaptive immune responses. Pattern recognition receptors (PRR) detect the presence of invading pathogens and are paramount in innate instruction of the adaptive immune response. A diverse class of PRRs, the NOD-like Receptors (NLR), has recently been implicated in the regulation of processes ranging from anti-tumor immunity to the adjuvant action of aluminum hydroxide. In this review we will highlight many of the recent findings in the NLR field with a particular focus on NLR influence of adaptive immune responses.

Figure 1

Stages of NLRP3 Inflammasome Activation. Under resting conditions, NLRP3 and pro-IL-1β are not highly expressed. By contrast, ASC and caspase-1 are constitutively expressed, although with different subcellular localization. Upon stimulation by a variety of stimuli, such as LPS and other PAMPs as well as IL-1β and other cytokines that trigger NF-κB activation (Signal 1), NLRP3 and pro-IL-1β are transcribed but not activated; this has been termed ‘licensing of the inflammasome’. Only after a specific NLRP3 trigger such as crystals, extracellular ATP or pore-forming toxins (Signal 2), is the inflammasome formed and activated, resulting in cleavage of numerous secreted proteins, including IL-1β. It should be noted that while numerous triggers of NLRP3 have been identified, the actual ligand that binds to NLRP3 (X in panel 3) has not been identified.