Role of Immune Cells and Cytokines for Immune Response in Kala-Azar

Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, central to which is the activation of targeted T-cell populations for appropriate cytokine production and activation of infected cells. There is a correlation between the clinical outcome of Leishmania infection and the cytokine response profile. While a protective immune response against Leishmania has been clearly identified to be related to the influence of a type-l response and IFN-γ production, the precise role of T helper (TH) 2 cytokines in non-healing infections requires further exploration. Experimental evidence and clinical studies indicate multifaceted role of various factors leading to parasite survival and multiplication. In early stage of infection, generation of reactive oxygen and nitrogen intermediates play significant role in curtailing the parasite multiplication. In later phase, hepatic resistance is expressed by the dominant role played by nitric oxide synthase (NOS)-2 gene regulation and on the other hand, production of inhibitors of NOS-2 gene expression, interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) correlate well with reduced parasite killing. The hepatic infection is usually self-limiting due to production of multiple cytokine responses including moderate level of tumour necrosis factor (TNF) but in spleen excess TNF mediates destructive pathology. CD8+ T cells appear to play multiple roles comprising both cytotoxic activity and secretion of cytokines and chemokines. A better understanding of the innate and acquired immune functioning of the host could aid in rational control and better therapeutic intervention of the disease.