A Novel Form of Macrophage Function Inhibition by Leishmania mexicana Infection: Involvement in Inhibition of NF-kB Translocation

Manipulation of host cell signalling pathways and pro-inflammatory proteins expression by Leishmania is critical for Leishmanias survival and resultant pathology. Therefore, the characteristics of long time exposure of promastigotes mediated signalling to the MAP kinases, COX-2, iNOS, NO production and NF-B pathways were investigated in comparison to LPS stimulation. Promastigotes caused no effect on phosphorylation of the three MAP kinases. Unlike outcome was observed on COX-2, iNOS and NO production using the same manner. Consequently, expressions of these proteins were also NF-B dependent. Surprisingly, promastigotes inhibit macrophage NF-B translocation into nucleus following LPS stimulation and caused a reversal of promastigotes mediated inhibition of macrophage COX-2, iNOS and NO production. These data demonstrated for the first time the role of NF-B translocation in mediating the effect of L. mexicana promastigotes on pro-inflammatory proteins which these proteins play a crucial role in innate immunity against Leishmania infection.