Leishmania infantum LeIF and its recombinant polypeptides modulate interleukin IL‐12p70, IL‐10 and tumour necrosis factor‐α production by human monocytes

SUMMARY Leishmania eukaryotic initiation factor (LeIF) antigen, aLeishmania protein, was shown to induce IL-12, IL-10 andtumour necrosis factor-a (TNF-a) production by humanmonocytes-derived macrophages and dendritic cells fromhealthy individuals. This cytokine-inducing activity was pre-viously found to be located in the amino-terminal region ofLeIF protein. This study aimed at characterizing the cyto-kine-inducing activity of Leishmania infantum LeIF [Leish-mania (L.) infantum (LieIF)] and at defining thefragments necessary for inducing cytokine secretion. Elevenrationally designed recombinant polypeptides, correspondingto the entire LeIF protein or parts of it, were expressed andused to stimulate monocytes from healthy individuals. Leish-mania (L.) infantum was able to induce IL-12p70, IL-10and TNF-a secretion in human monocytes. In addition, bothamino- (1–226) and carboxyl-terminal (196–403) parts ofthe protein were shown to induce significant levels of thethree cytokines analysed. However, IL-12p70-inducing activ-ity was not significant when monocytes were stimulated withthe fragments 129–226 and 129–261, inferring thatIL-12p70-inducing activity was primarily located withinamino acids 1–129 and 261–403. Although the full-lengthLieIF protein was a more potent inducer than the testedfragments, a significant cytokine-inducing activity was main-tained in smaller amino acid regions. This work suggeststhat cytokine-inducing activity of LieIF or its parts could beexploited in vaccination or immunotherapy protocols.Keywords cytokine, Leishmania eukaryotic initiation factor,leishmaniasis, monocytes