Chapters authored
Role of cAMP Homeostasis in Intra-Macrophage Survival and Infectivity of Unicellular Parasites like Leishmania
Unicellular eukaryotic pathogen Leishmania donovani, an intra-macrophage protozoan parasite, on exposure to phagolysosome conditions (PC) of mammalian macrophages, show increased cAMP level and cAMP-dependent protein kinase A (PKA) resulting in resistance to macrophage oxidative burst. In order to have a comprehensive understanding of cAMP signaling and their contribution to infectivity, studies were carried out on all the enzymes associated with cAMP metabolism such as adenylate cyclase, phosphodiesterase, pyrophosphatase and the regulatory and catalytic subunits of PKA. This chapter deals in detail the contribution of these components of cAMP signaling in cAMP homeostasis of the parasite as well as their role on successful host-parasite interaction leading to intracellular parasite survival and establishment of infection. Finally, a discussion is made about how these observations might be exploited for developing drug candidates targeting parasite specific features.
Part of the book: Vector-Borne Diseases
The Tale of Mastering Macrophage Environment through the Control of Inflammasome-Mediated Macrophage Activation and cAMP Homeostasis by the Protozoan Parasite Leishmania
Leishmania, being an intelligent protozoan parasite, modulates the defensive arsenals of the host to create a favorable niche for their survival. When the intracellular parasite is encountered by the host, multimeric complexes of inflammasomes get assembled and activated, thereby leading to genesis of inflammatory response. In order to subvert host defensive strategies, Leishmania utilizes their cyclic adenosine monophosphate (cAMP) and cAMP-induced response to neutralize macrophage oxidative damage. In this chapter, we summarize our current understanding of the mechanisms of inflammasome activation in macrophages and cAMP homeostasis of the parasite, leading to parasite viability within the macrophages and establishment of infection. Furthermore, we took into account, recent progresses in translating these research areas into therapeutic strategies, aimed at combating macrophage associated diseases.
Part of the book: Macrophages