The immune response to Leishmania: mechanisms of parasite control and evasion

After transmission of Leishmania parasites by sandflies, disease manifestation of the infection requires mechanisms which allow the parasites to replicate in the mammalian host and to resist, at least initially, its innate and acquired antileishmanial defence. Likewise, lifelong persistence of Leishmania parasites, as it occurs even in cases of clinical healing of the infection, points to the existence of strategies which enable the parasite to partially circumvent the protective adaptive immune response of the host. In this review we will discuss the mechanisms which can be invoked to contribute to the initial, as well as long-term, survival of Leishmania parasites in the host organism. These include the passive protection of the parasite against antileishmanial products and the retreat into "safe target cells", the active suppression of the synthesis of reactive oxygen or nitrogen intermediates, the modulation of the host cytokine response, the inhibition of antigen-presentation and T cell-stimulation, and the induction and expansion of counterprotective T helper cells. It is probable that none of these mechanisms alone is sufficient to guarantee the survival of Leishmania, but together they might provide the safe environment which protects the parasite from elimination.