title: Leishmania infantum LeIF and its recombinant polypeptides modulate interleukin IL-12p70, IL-10 and tumour necrosis factor-α production by human monocytes.
abstract: Leishmania eukaryotic initiation factor (LeIF) antigen, a Leishmania protein, was shown to induce IL-12, IL-10 and tumour necrosis factor-α (TNF-α) production by human monocytes-derived macrophages and dendritic cells from healthy individuals. This cytokine-inducing activity was previously found to be located in the amino-terminal region of LeIF protein. This study aimed at characterizing the cytokine-inducing activity of Leishmania infantum LeIF [Leishmania (L.) infantum (LieIF)] and at defining the fragments necessary for inducing cytokine secretion. Eleven rationally designed recombinant polypeptides, corresponding to the entire LeIF protein or parts of it, were expressed and used to stimulate monocytes from healthy individuals. Leishmania (L.) infantum was able to induce IL-12p70, IL-10 and TNF-α secretion in human monocytes. In addition, both amino- (1-226) and carboxyl-terminal (196-403) parts of the protein were shown to induce significant levels of the three cytokines analysed. However, IL-12p70-inducing activity was not significant when monocytes were stimulated with the fragments 129-226 and 129-261, inferring that IL-12p70-inducing activity was primarily located within amino acids 1-129 and 261-403. Although the full-length LieIF protein was a more potent inducer than the tested fragments, a significant cytokine-inducing activity was maintained in smaller amino acid regions. This work suggests that cytokine-inducing activity of LieIF or its parts could be exploited in vaccination or immunotherapy protocols.
authors.affiliation: Laboratoire d'Epidémiologie et d'Ecologie Parasitaire, Institut Pasteur de Tunis, Tunis-Belvedère, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Barhoumi
authors.forename: A
authors.initials: A
authors.lastname: Garnaoui
authors.forename: B
authors.initials: B
authors.lastname: Kaabi
authors.forename: N K
authors.initials: NK
authors.lastname: Tanner
authors.forename: I
authors.initials: I
authors.lastname: Guizani
mesh_terms: D001782:Blood Donors; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D018314:Leishmania infantum / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000469:parasitology*; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D010448:Peptide Initiation Factors / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D017384:Sequence Deletion; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: C508609:IL10 protein, human; C092810:LeIF protein, Leishmania; D050505:Mutant Proteins; D010448:Peptide Initiation Factors; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12