Characterization of the protein tyrosine phosphatase LmPRL-1 secreted by Leishmania major via the exosome pathway

Similar to other intracellular pathogens, Leishmania parasites are known to evade the antimicrobial effector functions of host immune cells. To date, however, only few virulence factors have been described for Leishmania (L.) major, one of the causative agents of cutaneous leishmaniasis. Here, we characterized the expression and function of a L. major phosphatase which we termed LmPRL-1. This enzyme shows a strong structural similarity to the human phosphatases of regenerating liver (PRL-1, -2, and -3) that are regulating the proliferation, differentiation and motility of cells. The biochemical characterization of the L. major phosphatase revealed that the enzyme is redox-sensitive. When analyzing the subcellular localization of the LmPRL-1 in promastigotes, amastigotes and within infected macrophages, we found that this phosphatase was predominantly expressed and secreted by promastigotes via the exosome route. Finally, we observed that ectopic expression of LmPRL-1 in L. major led to an increased number of parasites in macrophages. From these data, we conclude that the L. major phosphatase LmPRL-1 contributes to the intracellular survival of the parasites in macrophages.