Leishmania Exploits Host's Defence Machineries for Survival: A Tale of Immune Evasion
Amrita Saha and Anindita Ukil
from: Molecular Biology of Kinetoplastid Parasites (Edited by: Hemanta K. Majumder). Caister Academic Press, U.K. (2018) Pages: 97-110.
The disease Leishmaniasis caused by protozoan parasite of genus Leishmania, is a major health concern as over 12 million people are affected worldwide. The disease comprises of spectrum of clinical manifestations ranging from self-healing cutaneous lesions to life threatening infection of visceral organs to death. The lifestyle of Leishmania is that of an obligate intracellular parasite that resides and multiplies within the phagolysosome of host macrophages. Interestingly, these macrophages are the sentinels of the immune system,that are specialized for the destruction of invading pathogens. Therefore, in order to successfully dwell within its niche, Leishmania has had to evolve range of sophisticated mechanisms to subvert normal macrophage functioning. There are multiple ways by which intracellular pathogens like Leishmania make use of host cell's machinery in order to survive and replicate, either by employing strategies to inhibit proteins that play a positive role in immune cell activation or by activating molecules that act as negative regulators of immune cell signalling and function. Current research has focused on parasite induced alteration of host cell signalling pathways, combating microbicidal free radical generation and modulation of cytokine/chemokine profiles that alter immune cell activation and antigen presentation. The aim of this chapter is to highlight the molecular mechanisms underlying immune evasion strategies whereby Leishmania can subvert host surveillance, thereby exploiting the macrophage environment in its favour for its persistence. Understanding these mechanisms in detail may open up new perspectives on potential molecular pathways that are prone to pharmacological manipulation and can prove as promising areas for preclinical and clinical research read more ...