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