Flagellin as an adjuvant: cellular mechanisms and potential

Abstract

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.

FIGURE 1

Cellular mechanisms for the adjuvant effect of flagellin. The major cellular targets of flagellin are CD11c⁺ cells, cytokine- and chemokine-producing nonlymphoid cells, and T cells. The cumulative effect of the activation of these cell types results in enhanced activation of B cells and the generation of plasma and memory cells. The short thick arrows represent activation events. The binding of the flagellin-Ag X fusion to B cells does not result in a flagellin-mediated activation event but is linked to the normal response of the B cell upon binding its cognate Ag.