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Chapter 18 : Cytokines and Macrophages and Dendritic Cells: Key Modulators of Immune Responses
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
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This chapter discusses the fundamental role of phagocytes, with specific emphasis on macrophages and dendritic cells (DCs), as potent cytokine producers and responders, establishing them as primary effector cells as well as regulators of innate and adaptive immune responses. It draws attention to the role of T-cell-derived cytokines produced during adaptive Th1 and Th2 responses, IFN-γ and IL-4/IL-13, respectively, and their fundamental role in modulating macrophage and DC function. The chapter also discusses the cellular and molecular mechanisms that enable macrophages and DCs to express complex cytokine patterns in response to pathogens, which are key to mounting effective innate and downstream adaptive immune responses. The cellular response induced by the engagement of PRRs is often referred to as the “innate” activation of phagocytes, in contrast to the “classical” and “alternative” activation of macrophages by cytokines. IL-4 and IL-13 also induce intracellular enzymes that are implicated in cell recruitment and granuloma formation. Therefore, the distinctive macrophage phenotype induced by the Th2-type cytokines IL-4 and IL-13, also referred to as alternatively activated macrophages, plays an important role in dampening classical cell-mediated immune responses while reprogramming the response toward an appropriate type that promotes an efficient eradication of extracellular pathogens. Recognition of microorganisms or their products initiates complex signaling pathways in these cells that determine the pattern of cytokines produced and the subsequent effector response, critical for the eradication of pathogens with minimum damage to the host.
Key cytokines, produced by or exerting their effects on macrophages and DCs, regulate, direct, and balance the innate and adaptive immune response against pathogens. Gray arrows, stimulatory signals; broken lines, inhibitory signals.