9368620

pubmed:Citation

10

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.

eng

IM

MEDLINE

0014-2980

Print

NLM

2634-42

pubmed-meshheading:9368620-Adjuvants, Immunologic, pubmed-meshheading:9368620-Animals, pubmed-meshheading:9368620-Antigen-Presenting Cells, pubmed-meshheading:9368620-Antigens, CD80, pubmed-meshheading:9368620-CD40 Ligand, pubmed-meshheading:9368620-Cells, Cultured, pubmed-meshheading:9368620-Dendritic Cells, pubmed-meshheading:9368620-Gene Expression Regulation, pubmed-meshheading:9368620-Humans, pubmed-meshheading:9368620-Intercellular Adhesion Molecule-1, pubmed-meshheading:9368620-Interleukin-10, pubmed-meshheading:9368620-Interleukin-12, pubmed-meshheading:9368620-Leishmania major, pubmed-meshheading:9368620-Lipopolysaccharides, pubmed-meshheading:9368620-Macrophages, pubmed-meshheading:9368620-Membrane Glycoproteins, pubmed-meshheading:9368620-Peptide Initiation Factors, pubmed-meshheading:9368620-Protozoan Proteins, pubmed-meshheading:9368620-Staphylococcus aureus, pubmed-meshheading:9368620-Tumor Necrosis Factor-alpha, pubmed-meshheading:9368620-Up-Regulation

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.

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