HCV-infected cells and differentiation increase monocyte immunoregulatory galectin-9 production
| Autor: | Linling Cheng, Hugo R. Rosen, Noah M. K. Harwood, John A. Mengshol, Lucy Golden-Mason |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
animal structures Galectins viruses Hepatitis C virus Immunology Translational & Clinical Immunology Cell Communication Biology Exosomes medicine.disease_cause Exosome Monocytes Virus Flow cytometry 03 medical and health sciences otorhinolaryngologic diseases medicine Humans Immunology and Allergy RNA Messenger Cells Cultured medicine.diagnostic_test Macrophages Monocyte Toll-Like Receptors Cell Differentiation Cell Biology Hepatitis C medicine.disease Virology Molecular biology Microvesicles stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Apoptosis Hepatocytes |
| Zdroj: | Journal of Leukocyte Biology. 99:495-503 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.5a1214-582r |
| Popis: | The lectin galectin-9 may help establish and maintain chronic hepatitis C virus infection. Galectin-9 is elevated in the liver and sera of hepatitis C virus patients, induces apoptosis of hepatitis C virus-specific T cells, and increases inhibitory regulatory T cells. Kupffer cells stain strongly for galectin-9 protein in hepatitis C virus patients. In the current study, we determined stimuli that induce galectin-9 production by monocytes and macrophages in hepatitis C virus infection. With the use of real-time PCR and flow cytometry, we analyzed galectin-9 mRNA and protein from human monocytes cocultured with hepatitis C virus-infected cells or noninfectious hepatitis C virus subgenomic replicon cells. We focused on finding the stimuli for galectin-9 production. Additionally, we measured galectin-9 during monocyte-to-macrophage maturation. Finally, we examined galectin-9 in peripheral monocytes from hepatitis C virus patients using flow cytometry. Galectin-9 mRNA increased 8-fold when primary monocytes were exposed to hepatitis C virus--infected cells. Maximum induction required proximity or contact and did not require IFN-γ or hepatitis C virus virions. Coculture of monocytes with subgenomic replicon cells increased galectin-9 5-fold, and purified exosomes from infected cells stimulated galectin-9 production. Stimulation of monocyte TLR3, -7, and -8 increased galectin-9 production. Differentiation of monocytes to macrophages increased galectin-9, and nonclassic monocytes from hepatitis C virus patients had the highest levels of galectin-9. Hepatitis C virus-infected cells stimulated monocytes to produce galectin-9 in close proximity, possibly, in part, as a result of exosomes and endosomal TLRs. Differentiation of monocytes to macrophages increased galectin-9. Nonclassic monocytes from hepatitis C virus patients express the highest galectin-9 levels, suggesting they may contribute to elevated galectin-9 and adaptive immune inhibition in hepatitis C virus infection. |
| Databáze: | OpenAIRE |
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