Controlling the Toll road to dendritic cell polarization

The activation of dendritic cells (DC) via Toll-like receptors (TLRs) plays a decisive role in shaping the outcome of primary immune responses. Following TLR engagement by microbial products, DC migrate from peripheral tissues to lymphoid organs and up-regulate major histocompatibility complex and costimulatory molecules, acquiring the unique capacity to prime pathogen-specific, naive T cells. In addition, DC determine the character of the ensuing immune response by secreting cytokines that drive the development of T cells into T helper cell type 1 (Th1), Th2, or T regulatory effector cells. Three major factors influence the pattern of cytokines released by DC and accordingly, the Th balance: the lineage to which DC belong; the maturation stimulus; and inflammatory mediators present at the site of infection. A major focus of this review is the capacity of DC to integrate these factors and elicit distinct classes of immune responses.