Alum Induces Innate Immune Responses through Macrophage and Mast Cell Sensors, But These Sensors Are Not Required for Alum to Act As an Adjuvant for Specific Immunity

TLDR

The study investigates how the body recognizes alum by characterizing early innate and adaptive immune responses in mice injected with the adjuvant. The authors examined the early innate and adaptive responses in alum‑injected mice, focusing on cellular infiltration and cytokine production. Alum rapidly induces a type‑2 innate response, recruiting eosinophils, monocytes, neutrophils, dendritic cells, NK and NKT cells, and producing multiple cytokines and chemokines (including IL‑1β and IL‑5); while macrophage and mast‑cell–dependent cytokine production contributes to eosinophil recruitment, the adjuvant’s ability to prime CD4/CD8 T cells, elicit antibody responses, and bias toward Th2 is independent of these cells, inflammasome activation, or NLRP3.

Abstract

To understand more about how the body recognizes alum we characterized the early innate and adaptive responses in mice injected with the adjuvant. Within hours of exposure, alum induces a type 2 innate response characterized by an influx of eosinophils, monocytes, neutrophils, DCs, NK cells and NKT cells. In addition, at least 13 cytokines and chemokines are produced within 4 h of injection including IL-1beta and IL-5. Optimal production of some of these, including IL-1beta, depends upon both macrophages and mast cells, whereas production of others, such as IL-5, depends on mast cells only, suggesting that both of these cell types can detect alum. Alum induces eosinophil accumulation partly through the production of mast cell derived IL-5 and histamine. Alum greatly enhances priming of endogenous CD4 and CD8 T cells independently of mast cells, macrophages, and of eosinophils. In addition, Ab levels and Th2 bias was similar in the absence of these cells. We found that the inflammation induced by alum was unchanged in caspase-1-deficient mice, which cannot produce IL-1beta. Furthermore, endogenous CD4 and CD8 T cell responses, Ab responses and the Th2 bias were also not impacted by the absence of caspase-1 or NLRP3. These data suggest that activation of the inflammasome and the type 2 innate response orchestrated by macrophages and mast cells in vivo are not required for adjuvant effect of alum on endogenous T and B cell responses.