Chronic Hepatitis C Virus Infection Impairs M1 Macrophage Differentiation and Contributes to CD8+ T-Cell Dysfunction
Abstract
1. Introduction
2. Methods
2.1. Study Groups
2.2. Isolation of Monocytes and Generation of Macrophage Subsets
2.3. Macrophage Subset Phenotyping by Flow Cytometry
2.4. Quantification of Secreted Cytokines
2.5. Macrophage:CD8+ T-Cell Co-Culture
2.6. CD8+ T-Cell Functions
Quantification of IFN-γ+ and Perforin+ Cells and Detection of Degranulating (CD107a+) Cells
2.7. Statistical Analysis
3. Results
3.1. Altered Phenotypic Surface Marker Expression on Macrophage Subsets from Chronic HCV-Infected Patients
3.2. Altered Pro- and Anti-Inflammatory Cytokine Expression on Macrophage Subsets from HCV-Infected Patients
3.2.1. M1 Cells Acquire Cytokine Secretion Features of M2 Cells in HCV+(F3-4) Individuals
3.2.2. M2 Cells Acquire Cytokine Secretion Features of M1 Cells in HCV+(F3-4) Individuals
3.3. M1 Macrophages Enhance CD8+ T-Cell Functions in Normal Healthy Individuals via Contact-Dependent Mechanisms
3.4. M1 Macrophages Inhibit IFN-γ Expression on CD8+ T-Cells in Chronic HCV Infection
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Healthy Controls | HCV+ (F0-2)1 | HCV+ (F3-4)2 | |
---|---|---|---|
Number | 13 | 9 | 4 |
Age, avg. years (SD3) | 31.2 (8.4) | 50 (14.9) | 56.5 (4.1) |
Race | Caucasian | Caucasian (7), East Indian (1), African (1) | Caucasian (3), Native (1) |
HCV-RNA (IU/mL) | 3.1 × 106 (2.2 × 106) | 1.6 × 106 (2.2 × 106) | |
HCV genotype4 (n) | 1 (7: 1a n = 3, 1b n = 1), 2b (1) | 1a (3), 3 (1) | |
Fibroscan, avg. kPa5 (SD) | 6.1 (1.9) | 19.3 (7.1) | |
AST6 (U/L) | 25.4 (12.9) | 47.3 (37.3) | |
ALT7 (U/L) | 47.3 (23.6) | 75.0 (42.0) |
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Ahmed, F.; Ibrahim, A.; Cooper, C.L.; Kumar, A.; Crawley, A.M. Chronic Hepatitis C Virus Infection Impairs M1 Macrophage Differentiation and Contributes to CD8+ T-Cell Dysfunction. Cells 2019, 8, 374. https://doi.org/10.3390/cells8040374
Ahmed F, Ibrahim A, Cooper CL, Kumar A, Crawley AM. Chronic Hepatitis C Virus Infection Impairs M1 Macrophage Differentiation and Contributes to CD8+ T-Cell Dysfunction. Cells. 2019; 8(4):374. https://doi.org/10.3390/cells8040374
Chicago/Turabian StyleAhmed, Faria, Andrea Ibrahim, Curtis L. Cooper, Ashok Kumar, and Angela M. Crawley. 2019. "Chronic Hepatitis C Virus Infection Impairs M1 Macrophage Differentiation and Contributes to CD8+ T-Cell Dysfunction" Cells 8, no. 4: 374. https://doi.org/10.3390/cells8040374
APA StyleAhmed, F., Ibrahim, A., Cooper, C. L., Kumar, A., & Crawley, A. M. (2019). Chronic Hepatitis C Virus Infection Impairs M1 Macrophage Differentiation and Contributes to CD8+ T-Cell Dysfunction. Cells, 8(4), 374. https://doi.org/10.3390/cells8040374