Flagellin as an Adjuvant: Cellular Mechanisms and Potential

Flagellin is a potent activator of a broad range of cell types involved in innate and adaptive immunity. An increasing number of studies have demonstrated the effectiveness of flagellin as an adjuvant, as well as its ability to promote cytokine production by a range of innate cell types, trigger a generalized recruitment of T and B lymphocytes to secondary lymphoid sites, and activate TLR5(+)CD11c(+) cells and T lymphocytes in a manner that is distinct from cognate Ag recognition. The plasticity of flagellin has allowed for the generation of a range of flagellin-Ag fusion proteins that have proven to be effective vaccines in animal models. This review summarizes the state of our current understanding of the adjuvant effect of flagellin and addresses important areas of current and future research interest.