Leishmania is the causative protozoan parasite of leishmaniasis. Distinct species provoke localized/diffuse cutaneous leishmaniasis or visceral leishmaniasis. Leishmania parasites have developed diverse strategies to evade the host immune response expressed through various cells, especially macrophages, NK cells, and dendritic cells. Participating in some of these strategies are Leishmania surface molecules, such as lipophosphoglycan (LPG) and protease gp63, which are thus considered virulence factors. LPG has been shown to modulate proinflammatory responses. For example, L. major LPG activates NK cells through toll-like receptor-2 (TLR2), while L. mexicana LPG elicits a differential production of cytokines in human dendritic cells and monocytes. Moreover, L. mexicana LPG activates MAP kinases in macrophages, which in turn enhance proinflammatory cytokine production through TLRs. Additionally, Leishmania exosomes have been found to strongly affect macrophage signaling and functions. Furthermore, proteins secreted by Leishmania promastigotes and amastigotes modulate the production of proinflammatory cytokines in human macrophages. Since Leishmania is an obligate intracellular parasite, its promastigotes utilize several mechanisms to survive and duplicate inside host cells, including the inhibition of apoptosis. It is now clear that MAPK p38, JNK, ERK 1/2, and PI3K/Akt participate in the inhibition of both natural and induced apoptosis of macrophages, neutrophils, and dendritic cells.
Part of the book: Leishmaniases as Re-emerging Diseases
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.
Part of the book: Current Understanding of Apoptosis
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.
Part of the book: Dendritic Cells
Trypanosoma cruzi is the causal agent of Chagas disease that affects 6–7 million people around the world, principally in Latin America. This disease is characterized for the presence of an acute phase in which the host immune response plays a central role in the elimination of the parasite. If the parasite is not efficiently eliminated, patients can remain asymptomatic or develop a chronic infection. One of the cells that are primarily infected with this intracellular parasite is macrophages (Mϕ). Mϕ present a wide array of activation states with classically activated macrophages in one pole (CAMϕ) and alternatively activated macrophages (AAMϕ) in the other. One of the most important differences between these two activation states is the presence of the inducible nitric oxide synthase (iNOS or NOS2) in CAMϕ and arginase 1 (Arg-1) in AAMϕ; both enzymes share the same substrate, l-arginine, and are reciprocally regulated by the action of Th1 cytokines in the case of NOS2 and Th2 cytokines in the case of Arg-1. The activation of CAMϕ permits the production of nitric oxide (NO), highly trypanotoxic, while the activation of AAMϕ allows the synthesis of polyamines, necessary for parasite duplication. l-arginine is a very important metabolite situated in the center between the elimination and perpetuation of T. cruzi.
Part of the book: Biology of Trypanosoma cruzi