NLRP3 inflammasome (NLR family pyrin domain containing 3) (NLRP3)

The innate immune pattern-recognition pathways stimulated by Alum adjuvant primarily center on the activation of the NLRP3 inflammasome, a multi-protein complex essential for sensing sterile stressors and pathogens (Eisenbarth et al., 2008). Alum (aluminum hydroxide or phosphate) functions by inducing the release of damage-associated molecular patterns (DAMPs), such as uric acid and host DNA, from stressed or dying cells (Kool et al., 2008). Upon phagocytosis, Alum crystals cause lysosomal destabilization and the release of cathepsin B, which serves as a trigger for NLRP3 assembly (Hornung et al., 2008). The assembled NLRP3 inflammasome recruits the adapter protein ASC and pro-caspase-1, leading to the proteolytic activation of caspase-1, which then processes the pro-inflammatory cytokines IL-1β and IL-18 into their mature forms (Li et al., 2008). These cytokines create a local inflammatory environment that enhances the recruitment of antigen-presenting cells and promotes a robust Th2-biased adaptive immune response. Additionally, Alum-induced DNA release can activate the STING (Stimulator of Interferon Genes) pathway, further contributing to its adjuvant properties (Marichal et al., 2011). While Alum is the most widely used vaccine adjuvant globally, its activation of these pathways is also implicated in the pathogenesis of various autoinflammatory and metabolic diseases.

Other names

CryopyrinNALP3CIAS1PYPAF1Caspase recruitment domain-containing protein 7Alum-responsive pathwayAluminum-induced pattern-recognition pathway

Alum stimulates innate immune pathways by inducing lysosomal rupture and the release of endogenous danger signals like uric acid and DNA, which trigger the NLRP3 inflammasome and STING pathways to promote cytokine secretion and adaptive immunity.