Dendritic Cell Subsets and Toll-Like Receptors

Toll-like receptors exist as highly conserved pathogen sensors throughout the animal kingdom and they represent a key family of molecules bridging the ancient innate and adaptive immune systems. The first molecules of adaptive immunity appeared in the cartilaginous fishes and, with these, major histocompatibility proteins and cells expressing these molecules, and thus, by definition, the advent of antigen-presenting cells and the “professional” antigen-presenting cells, the dendritic cells. Dendritic cells themselves are highly specialized subsets of cells with the major roles of antigen presentation and stimulation of lymphocytes. The dendritic cell functions of inducing immunity are regulated by their own activation status, which is governed by their encounter with pathogen-associated molecular patterns that signal through pattern recognition receptors, including Toll-like receptors, expressed at the surface and within the cytoplasm and endosomal membranes of dendritic cells. Thus although dendritic cells play a crucial role in the induction of adaptive immunity, the adaptive response is itself initiated at the level of ancient receptors of the innate immune system. A further degree in the complexity of dendritic cell activation is established by the fact that not all dendritic cells are equal. Dendritic cells exist as multiple subsets that vary in location, function, and phenotype. Distinct dendritic cell subsets display great variation in the type of Toll-like receptors expressed and consequently variation in the type of pathogens sensed and the subsequent type of immune responses initiated.