Conventional dendritic cells are abundant at barrier tissue sites, such as the intestines, lung, and skin, where they are in close contact with surface epithelia. They are also present in most solid organs such as the heart and kidneys. In the absence of infection or tissue injury, dendritic cells have low levels of co-stimulatory molecules, and so are not yet equipped to stimulate naive T cells. Like macrophages, dendritic cells are very active in ingesting antigens by phagocytosis using complement receptors and Fc receptors (which recognize the constant regions of antibodies in antigen:antibody complexes), and C-type lectins, which recognize carbohydrates and on dendritic cells include the mannose receptor, DEC 205, langerin, and Dectin-1. Other extracellular antigens are taken up nonspecifically by the process of macropinocytosis, in which large volumes of surrounding fluid are engulfed. In this way microbes that have evolved strategies to escape recognition by phagocytic receptors, such as bacteria with thick polysaccharide capsules, can be ingested. The versatility in pathways for antigen uptake enables dendritic cells to present antigens from virtually any type of microbe, including fungi, parasites, viruses, and bacteria (Fig. 9.15). Uptake of extracellular antigens by these pathways directs them into the endocytic pathway, where they are processed and presented on MHC class II molecules (see Chapter 6) for recognition by CD4 T cells.
A second route of antigen handling by dendritic cells occurs when antigen directly enters the cytosol, for example, through viral infection. Dendritic cells are directly susceptible to infection by some viruses, which enter the cytoplasm by binding to cell-surface molecules that act as entry receptors. Viral proteins synthesized in the cytoplasm of dendritic cells are processed in the proteasome and presented on the cell surface as peptides loaded onto MHC class I molecules after transport into the endoplasmic reticulum, as in any other type of virus-infected cell (see Chapter 6). This enables dendritic cells to present antigen to and activate naive CD8 T cells, which then differentiate into cytotoxic effector CD8 T cells that recognize and kill any virus-infected cell.
Fig. 9.15 The different routes by which dendritic cells can take presentation to Cd8 T cells (third panel). It is possible, however, for up, process, and present protein antigens. uptake of antigens exogenous antigens taken into the endocytic pathway to be delivered into the endocytic system, either by receptor-mediated phagocytosis into the cytosol for eventual delivery to MhC class I molecules for or by macropinocytosis, is considered to be the major route for presentation to Cd8 T cells, a process called cross-presentation delivering peptides to MhC class II molecules for presentation to (fourth panel). Finally, it seems that antigens can be transmitted from Cd4 T cells (first two panels). production of antigens in the cytosol, one dendritic cell to another, particularly for presentation to Cd8 for example, as a result of viral infection, is thought to be the T cells, although the details of this route are still unclear (fifth panel). major route for delivering peptides to MhC class I molecules for