DAMPs and adjuvant

Vaccine adjuvants are increasingly recognized to modulate immune responses not through single pattern-recognition receptors, but through broader cellular stress responses that lead to innate immune activation. Damage-associated molecular patterns (DAMPs) play a central role in linking adjuvant-induced cellular perturbations to downstream immune signaling. In this review, we summarize current understanding of how cellular stress and cell death associated with adjuvant administration result in the release of DAMPs, and how these signals are sensed by major innate immune pathways, including Toll-like receptors, cytosolic DNA sensing via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, and NLR family pyrin domain containing 3 (NLRP3) inflammasomes. We further discuss the role of DAMP-mediated signaling in dendritic cell activation and the subsequent regulation of adaptive immune responses. Finally, we introduce chitosan-based adjuvants as an example of materials that induce innate immune activation through DAMP-associated pathways, and discuss their implications for the rational design of future vaccine adjuvants.