Enhanced antigen uptake by dendritic cells induced by the B pentamer of the type II heat-labile enterotoxin LT-IIa requires engagement of TLR2

The potent mucosal adjuvant properties of the type II heat-labile enterotoxin LT-IIa of Escherichia coli are dependent upon binding of the B pentamer of the enterotoxin (LT-IIa-B5) to ganglioside receptors on immunocompetent cells. To evaluate the immunomodulatory activities of LT-IIa-B5, in vitro experiments employing bone marrow-derived dendritic cells (BMDC) were performed. Uptake of OVA-FITC, a model antigen (Ag), was enhanced by treatment of BMDC with LT-IIa-B5, but not by treatment of cells with the B pentamer of cholera toxin (CTB). Expression of co-stimulatory molecules (CD40, CD80, CD86, and MHC-II) and cytokines (IL-12p40, TNF-α, and IFN-γ) was increased in BMDC treated with LT-IIa-B5. The capacity of LT-IIa-B5 to enhance Ag uptake and to induce expression of co-stimulatory receptors and cytokines by BMDC was dependent upon expression of TLR2 by the cell. Increased Ag uptake induced by LT-IIa-B5 was correlated with increased Ag-specific proliferation of CD4+ T cells in an in vitro syngeneic DO11.10 CD4+ T cell proliferation assay. These experiments confirm that LT-IIa-B5 exhibits potent immunomodulatory properties which may be exploitable as a non-toxic mucosal adjuvant.