ALeishmania protein that modulates interleukin (IL)-12, IL-10 and tumor necrosis factor-α production and expression of B7-1 in human monocyte-derived antigen-presenting cells
| Autor: | Steven G. Reed, Kenneth H. Grabstein, Michelle Steeves, Probst Peter, Ana L. Gervassi, Yasir A. W. Skeiky |
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| Rok vydání: | 1997 |
| Předmět: |
Lipopolysaccharides
Staphylococcus aureus CD40 Ligand Immunology Protozoan Proteins Antigen-Presenting Cells Biology Adjuvants Immunologic Peptide Initiation Factors Interferon medicine Animals Humans Immunology and Allergy Antigen-presenting cell Cells Cultured Leishmania major Membrane Glycoproteins CD40 Tumor Necrosis Factor-alpha Macrophages Interleukin Dendritic Cells Dendritic cell Intercellular Adhesion Molecule-1 Interleukin-12 Molecular biology Interleukin-10 Up-Regulation Cell biology Interleukin 10 Gene Expression Regulation B7-1 Antigen Interleukin 12 biology.protein Tumor necrosis factor alpha medicine.drug |
| Zdroj: | European Journal of Immunology. 27:2634-2642 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.1830271024 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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