A critical step in the induction of adaptive immunity is the activation of dendritic cell maturation. When an infection occurs, dendritic cells capture pathogens by means of phagocytic receptors or macropinocytosis, and then activate responses to these pathogens through pattern recognition receptors such as TLRs (Fig. 9.17, top panel). Multiple members of the TLR family are expressed on tissue dendritic cells and are thought to be involved in detecting and signaling the presence of the various classes of pathogens (see Fig. 3.16). In humans, conventional dendritic cells express all known TLRs except for TLR-9, which is, however, expressed by plasmacytoid dendritic cells along with TLR-1 and TLR-7, and other TLRs to a lesser degree. In addition to the pattern recognition receptors described in Chapter 3, several of the phagocytic receptors used by dendritic cells to take up pathogens also provide maturation signals. Examples include the lectin DC-SIGN, which binds mannose and fucose residues present on a wide range of pathogens; and Dectin-1, which recognizes β-1,3-linked glucans found in fungal cell walls (see Fig. 3.2). Other receptors that can bind pathogens, such as receptors for complement, or phagocytic receptors such as the mannose receptor, may contribute to dendritic cell activation as well as to phagocytosis.
TLR signaling results in a significant alteration in the chemokine receptors expressed by dendritic cells, which facilitates their migration into secondary lymphoid tissues. This change in dendritic cell behavior is often called licensing, as the cells are now embarked on the program of differentiation that will enable them to activate T cells. TLR signaling induces expression of the receptor CCR7, which makes the activated dendritic cells sensitive to the chemokine CCL21 produced by lymphoid tissue and induces their migration through the lymphatics and into the local lymphoid tissues. Whereas T cells must cross the wall of high endothelial venules to leave the blood and reach the T-cell zones, dendritic cells entering via the afferent lymphatics migrate directly into the T-cell zones from the marginal sinus.