Role for IL-10 in inducing functional impairment of monocytes upon TLR4 ligation in patients with chronic HCV infections
| Autor: | Harry L.A. Janssen, Bi-Sheng Liu, Andre Boonstra, Zwier M. A. Groothuismink |
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| Přispěvatelé: | Gastroenterology & Hepatology |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Lipopolysaccharides Male Agonist medicine.drug_class Blotting Western Immunology Stimulation Hepacivirus Biology Monocytes Proinflammatory cytokine Immune system medicine Humans Immunology and Allergy RNA Messenger Cells Cultured Interleukin-12 Subunit p40 Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Imidazoles Cell Biology Hepatitis C Chronic Middle Aged Interleukin-10 Toll-Like Receptor 4 Interleukin 10 Toll-Like Receptor 8 Case-Control Studies Immune System Interleukin 12 TLR4 Cytokines Female Tumor necrosis factor alpha |
| Zdroj: | Journal of Leukocyte Biology, 89(6), 981-988. John Wiley & Sons Inc. |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.1210680 |
| Popis: | The consequences of chronic infection with the HCV on immunity to distinct pathogens are not fully appreciated, despite the potent modulatory effects of HCV on the immune system. We observed that upon TLR4 ligation, monocytes from chronic HCV patients demonstrated three to five times lower TNF and IL-12p40 production as compared with healthy individuals. However, augmented production of TNF, IL-12p40, and IL-12p70 by monocytes was observed upon stimulation with R848. Importantly, we observed that the levels of IL-10 in chronic HCV patients are higher in serum and that more IL-10 is produced by monocytes as compared with healthy individuals. The inhibitory effect of IL-10 on the production of proinflammatory cytokines by monocytes was only observed upon LPS stimulation but not upon R848 stimulation, showing that only the TLR4 pathway in monocytes is sensitive to the suppressive effects of IL-10. Interestingly, monocytes stimulated with the TLR4 agonist, but not TLR8 agonist, produced higher levels of IL-10 when exposed to patient serum as compared with serum from healthy individuals. Our results indicate that by differentially affecting TLR4 and TLR8 pathways, IL-10 may mediate highly selective modulation of the function of monocytes observed in chronic HCV patients. This suggests that there is no overall increased susceptibility to pathogens but a specific suppression of the functionality of TLR4 signaling pathway in monocytes, which is, at least partly, mediated via IL-10. |
| Databáze: | OpenAIRE |
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