期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 99, 期 3, 页码 495-503出版社
WILEY
DOI: 10.1189/jlb.5A1214-582R
关键词
JFH-1; non-classical monocyte; exosome
资金
- Denver Research Institute
- Liver Scholar Award from American Association for the Study of Liver Disease
- U.S. National Institutes of Health National Institute of Allergy and Infectious Diseases [R21-AI103361]
- American Liver Foundation
- VA Merit Review Grant
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-gamma 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.
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