Immunopathology of Leishmaniasis: An Update

Leishmaniasis represents a severe, increasing, public health problem. The perspective of its control is highly dependent on research progress, on therapeutic manipulations of the immune system, and on vaccine development. 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-1 response and IFN-γ production, the precise role of T helper (T_H) 2 cytokines in non-healing infections requires further exploration. IL-4 and IL-13 (T_H2 cytokines) can promote disease progression in cutaneous leishmaniasis, whereas IL-4 would appear to enhance protective type-1 responses in visceral leishmaniasis. Thus, the T_H1/T_H2 paradigm of resistance/susceptibility to intracellular parasites is probably an oversimplification of a more complicated network of regulatory/counter regulatory interactions. Moreover, the presence of antigen specific regulatory T cell subsets may provide an environment that contributes to the balance between T_H1 and T_H2 cells. Finally, the involvement of CD8⁺ T cells has been described, but the modality of their function in this kind of infection has not been so far elucidated.