Dendritic Cells

Dendritic cells perform essential recognition and effector roles in innate immunity. We introduced dendritic cells in Chapter 2, and their role in antigen presentation to T cells is discussed in Chapter 6. Recall that this heterogeneous family of bone marrow-derived cells with long dendrite-like cytoplasmic processes are constitutively present in epithelia and most tissues of the body. Because of their placement and morphology, these cells are poised to detect invading microbes. Furthermore, dendritic cells express more different types of TLRs and cytoplasmic pattern recognition receptors than any other cell type, making them the most versatile sensors of PAMPs and DAMPs among all cell types in the body. One particular subset of dendritic cells, called plasmacytoid dendritic cells because their morphology is similar to antibody-producing plasma cells, is the major source of antiviral cytokines, type I interferons, produced in response to viral infections. This feature of plasmacytoid dendritic cells is due in part to the fact that these cells, more than other cell types, abundantly express the endosomal TLRs (TLRs 3, 7, 8, 9) that recognize nucleic acids of viruses that have been internalized into the cell. We will discuss the antiviral actions of type I interferons in more detail later in the chapter.

Dendritic cells are uniquely capable of triggering and directing adaptive T cell-mediated immune responses, and this is dependent on their innate immune responses to microbes. This capability reflects the ability of dendritic cells to take up microbial protein antigens, to transport them to lymph nodes where naive T cells home, and to alter and display the protein antigens in a way that the T cells can recognize. These functions will be discussed in great detail in Chapter 6. Importantly, the innate response of dendritic cells to PAMPs is essential for these functions, which are enhanced by TLR signaling. Furthermore, TLR signaling induces dendritic cell expression of molecules, including costimulatory molecules and cytokines, that are needed, in addition to antigen, for the activation of the naive T cells and their differentiation into effector T cells. Depending on the nature of the microbe that induces the innate response, a dendritic cell will direct naive T cell differentiation into distinct types of effector cells, such as IFN-y-producing TH1 cells or IL-17-producing TH17 cells. The influence of dendritic cells on T cell activation and differentiation will be discussed further in Chapter 9.

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