Activation of dendritic cells and induction of CD4+ T cell differentiation by aluminum-containing adjuvants

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

“…44,45 Similarly, the significance of a depot of antigen at the injection site is still unclear; as is the effect on APCs. 21,22,24,25 In a recent study, aluminium, in the form of Imject Ò Alum, was shown to induce uric acid release at the injection site, leading to recruitment of inflammatory monocytes. 15 Similarly, we observed increased numbers of monocytes and macrophages after injection of Al(OH) 3 but we also found that the numbers were much lower than after injection of DDA/MPL and we did not observe increased numbers of mature DCs.…”

“…14 In a recent study, the aluminium-containing Imject Ò (Pierce Biochemicals) adjuvant recruited and activated inflammatory monocytes to the site of injection through the induction of uric acid, 15 and in the presence of TLR agonists aluminium induces inflammasome activation. [16][17][18] Aluminium salts induce Th2 differentiation and humoral immunity, 19,20 but the exact mechanism, as well as the dependence on the classical Th2-inducing cytokine, interleukin (IL)-4, remains unclear both in vitro [21][22][23][24][25] and in vivo. 26,27 In this respect it is a problem that negative results are rarely published because this may lead to an erroneous bias in the general view of how aluminium salts function as adjuvants.…”

The role of inflammasomes in the immunostimulatory effects of particulate vaccine adjuvants

“…Given the central role of APC, particularly DC, in linking innate to adaptive immunity, researchers have spent considerable effort investigating how alum influences APC biology. Surprisingly, alum is unable to directly activate DC in vitro in terms of upregulation of costimulatory molecules [4][5][6], although DC are activated indirectly by alum in vivo [5]. Despite a lack of DC maturation, alum does enhance Ag uptake and presentation [6][7][8][9].…”

“…In 2007 it was found that aluminium-containing adjuvants enhanced the activation of caspase 1 and release of IL-1b and IL-18 from murine DC [4] and human PBMC and DC in the presence of TLR agonists [5]. A number of articles then demonstrated that alum/TLR-induced inflammasome activation was dependent on NLRP3 and ASC [6,7].…”

The controversial relationship between NLRP3, alum, danger signals and the next‐generation adjuvants

“…Surprisingly, alum is unable to directly activate DC in vitro in terms of upregulation of costimulatory molecules [4][5][6], although DC are activated indirectly by alum in vivo [5]. Despite a lack of DC maturation, alum does enhance Ag uptake and presentation [6][7][8][9].…”