A Leishmania protein that modulates interleukin (IL)-12, IL-10 and tumor necrosis factor-alpha production and expression of B7-1 in human monocyte-derived antigen-presenting cells

Eur J Immunol. 1997 Oct;27(10):2634-42. doi: 10.1002/eji.1830271024.


LeIF, a gene homologue of the eukaryotic initiation factor 4A was first described as a leishmanial antigen that induced a Th1-type T cell response in peripheral blood mononuclear cells (PBMC) from leishmaniasis patients. Moreover, the interferon (IFN)-gamma production by PBMC was found to be interleukin (IL)-12 dependent. Herein, we characterize the effects of LeIF on cytokine production and expression of surface molecules by normal human monocytes as well as by monocyte-derived macrophages and dendritic cells (MoDC). LeIF was a strong inducer of IL-12 and, to a lesser extent, of IL-10 and tumor necrosis factor (TNF)-alpha in macrophages and MoDC. IL-12 production did not require CD40 triggering, confirming that the ability of LeIF to induce IL-12 was not mediated through an effect on T cells. However, addition of soluble CD40 ligand (L) synergistically augmented IL-12 production in macrophages and MoDC. The cytokine-inducing activity of LeIF is located in the N-terminal portion of the molecule and was both proteinase K sensitive and polymyxin B resistant. LeIF, lipopolysaccharide and fixed Staphylococcus aureus all induced comparable amounts of IL-12, validating the potent cytokine-inducing effects of LeIF. Moreover, of these stimuli, LeIF had the highest IL-12/IL-10 and IL-12/TNF-alpha ratio demonstrating the preference of LeIF for IL-12 induction. Studies investigating the expression of surface molecules showed that LeIF up-regulated B7-1 and CD54 (ICAM-1) on macrophages and MoDC. To our knowledge this is the first report describing IL-12 production, up-regulation of co-stimulatory and intercellular adhesion molecules by monocytic antigen-presenting cells in response to a protein from a pathogenic microorganism. These immunomodulatory characteristics of LeIF might be excellent properties for a Th1-type adjuvant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigen-Presenting Cells / drug effects*
  • Antigen-Presenting Cells / metabolism
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / genetics
  • CD40 Ligand
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Leishmania major / immunology*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Membrane Glycoproteins / pharmacology
  • Peptide Initiation Factors / pharmacology*
  • Protozoan Proteins / pharmacology*
  • Staphylococcus aureus / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation


  • Adjuvants, Immunologic
  • B7-1 Antigen
  • LeIF protein, Leishmania
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Peptide Initiation Factors
  • Protozoan Proteins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interleukin-10
  • CD40 Ligand
  • Interleukin-12