Nitric oxide induced expression of stress proteins in virulent and avirulent promastigotes of Leishmania donovani

Abstract

Intracellular survival and replication of Leishmania donovani inside macrophage is essential for establishment of the disease. Cytokines play an important role in this process through activation or inhibition of macrophage antimicrobial activity. Nitric oxide (NO) has been demonstrated to be the principal effector molecule mediating intracellular killing of Leishmania. We have examined the effect of NO and various other cytokines on stress protein synthesis by promastigotes of L. donovani virulent and avirulent strains. Virulent promastigotes exposed to NO showed appreciable increase in relative synthesis of HSPs 83, 70 and 65. The overexpression of HSPs on exposure of parasite to NO was observed to be more pronounced at 37°C than at 24°C. In contrast, the avirulent promastigotes responded by an increase in relative synthesis of HSP70 alone at 37°C. Furthermore, treatment of promastigotes of L. donovani with γIFN, TGF-β or IL-4 did not significantly alter the stress proteins expression. The overexpression of HSPs in promastigotes of L. donovani in response to sublethal doses of NO suggests that HSPs may be playing a protective role for parasite survival in the mammalian host. This is further supported by the observation that a significantly higher induction of HSPs is seen in the virulent as compared to the avirulent strain of L. donovani.