Immunity to pathogens requires generation of effective innate and adaptive immune responses. Leishmania donovani evades these host defense mechanisms to survive and persist in the host. A better understanding and identification of mechanisms that L. donovani employs for its survival is critical for developing novel therapeutic interventions that specifically target the parasite. This paper will highlight some of the mechanisms that the parasite utilizes for its persistence and also discuss how the immune response is regulated. 1. Introduction Visceral leishmaniasis (VL) is caused by the intracellular parasites Leishmania donovani and/or Leishmania infantum/chagasi. In the mouse model of visceral leishmaniasis, there is a distinct organ-specific pattern of parasite growth during the disease progression. Infection in the liver is characterized by a rapid increase in the parasite burden in the first 4 weeks of infection followed by clearance of the parasite within 6–8 weeks. This self-curing mechanism in the liver is attributed to the development of a Th1 dominated granulamatous response [1] characterized by high IFNγ production by CD4 and CD8 T cells. In contrast to liver, infection in the spleen has serious consequences demonstrated by increased parasite burden, disruption of splenic microarchitecture and impaired immune responses resulting in the establishment of parasite persistence [2]. Although the exact mechanism by which the parasite establishes chronic infections in the spleen still remains elusive, it is now becoming evident that the parasite targets and alters the functions of host immune system for evasion. Some of the mechanisms that are altered include suppression of host protective Th1 responses, generation of defective CD8 T cells and inhibition of dendritic cell (DC) functions [2–4]. In addition to modifying DC and T-cell function, the parasite also modulates B-cell function for its survival. Furthermore, by directly interacting with different cellular subsets, the parasite also generates an immunosuppressive environment by inducing IL-10 production and thus favoring its survival in the host. In the first part of this paper we will discuss the above mentioned mechanisms utilized by the parasite to evade host immune response and establish chronic infection in the spleen. The second part of the paper will focus on the L. donovani infection in the liver and the regulation of the inflammatory response in this organ. 2. Infection in the Spleen In the experimental model of VL, the spleen is a site of chronic inflammation, characterized by
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