Dendritic cells comprise a complex array of cell populations that play a leading role in immune defense. In an immature state, they have the capacity to sense and uptake different antigens. Upon capturing antigens, they become activated, mature, and migrate to lymph nodes where they present antigen-derived peptides to naïve T cells. Due to these excellent surveillance properties, dendritic cells play an important role against parasitic infections. Also, dendritic cells are an important source of IL-12, which is a fundamental proinflammatory cytokine in the control of intracellular parasites. The aim of this chapter is to review the most important characteristics and functions of dendritic cells and their role in the control of infection by parasites.
Apoptosis is a biological process carried out during maturation, remodeling, growth, and developmental processes in tissues, and also represents an important defense mechanism of cells against intracellular microorganisms. In counterpart, diverse intracellular pathogens have developed a wide array of strategies to evade apoptosis and persist inside cells. Apoptotic cell death can be triggered through different intracellular signaling pathways that lead to morphological changes and eventually cell death. Among these pathways, MAPK and PI3K play a central role. The precise control of the signaling pathways that lead to apoptosis is crucial for the maintenance of tissue homeostasis. Paradoxically, these same pathways are utilized during infection by distinct intracellular microorganisms in order to evade recognition by the immune system, inhibit apoptosis, and therefore survive, reproduce, and develop inside cells.
Dendritic cells (DC) along with macrophages are the main host cells of the intracellular parasite Leishmania. DC traverse a process of maturation, passing through an immature state with phagocytic ability to a mature one where they can modulate the immune response through the secretion of cytokines. Several studies have demonstrated that Leishmania inhibits DC maturation. Nevertheless, when cells are subjected to a second stimulus such as LPS/IFN-γ, they manage to mature. In the maturation process of DC, several signaling pathways have been implicated, importantly MAPK. On the other hand, Akt is a signaling pathway deeply involved in cell survival. Some Leishmania species have shown to activate MAPK and Akt in different cells. The aim of this work was to investigate the role of ERK and Akt in the maturation of monocyte-derived DC (moDC) infected with L. mexicana. moDC were infected with L. mexicana metacyclic promastigotes, and the phosphorylation of ERK and Akt, the expression of MHCII and CD86 and IL-12 transcript, and secretion were determined in the presence or absence of an Akt inhibitor. We showed that L. mexicana induces a sustained Akt and ERK phosphorylation, while the Akt inhibitor inhibits it. Moreover, the infection of moDC downregulates CD86 expression but not MHCII, and the Akt inhibitor reestablishes CD86 expression and 12p40 production. Thus, L. mexicana can modulate DC maturation though Akt signaling.