Innate immune sensors engaged by alum adjuvant

Innate immune sensors engaged by alum adjuvant refers to a collection of molecular complexes and signaling pathways that detect aluminum salts, the most widely used vaccine adjuvants. The primary and most well-characterized sensor is the NLRP3 inflammasome, which is activated following the phagocytosis of alum particles, leading to lysosomal destabilization and the release of cathepsins into the cytoplasm (Eisenbarth et al., 2008; Li et al., 2008). Beyond direct sensing, alum induces the release of endogenous danger-associated molecular patterns (DAMPs) such as host DNA, ATP, and uric acid, which are recognized by sensors like cGAS, P2X7, and NLRP3, respectively (Marichal et al., 2011; Kool et al., 2008). Alum also interacts directly with the plasma membrane of immune cells, triggering lipid raft reorganization and the activation of Syk and PI3K signaling pathways (Flach et al., 2011). These sensors collectively orchestrate the production of pro-inflammatory cytokines like IL-1β and IL-18, promote the recruitment of innate immune cells, and enhance the maturation of antigen-presenting cells, thereby boosting the adaptive immune response to the vaccine antigen.

Other names

NLRP3 inflammasomeNALP3 inflammasomeSyk kinasecGAS-STING pathwayP2X7 receptorAlum-responsive innate sensorsGPR92 (LPA5)

Activation of the NLRP3 inflammasome via lysosomal rupture and cathepsin release; induction of DAMP release (DNA, uric acid, ATP) which activates cGAS and P2X7; and direct membrane interaction leading to Syk and PI3K signaling.