1320. Interferon-alpha Treatment Triggers Swift Monocyte-to-Dendritic Cell Differentiation In Vivo in Treatment-Na´ve Patients with Chronic Hepatitis C Virus Infection
Session: Poster Abstract Session: Biomarkers and Correlates of Protection
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background:  Interferon-alpha (IFN-α) combined with ribavirin is the current standard-of-care treatment for chronic hepatitis C virus (HCV) infection. The effectiveness of this treatment varies among different patients and multiple host and viral factors have been implicated in the variability. IFN-α can act to eliminate infections via inhibiting viral replication directly or by modulating immunity. This study was designed to investigate the early innate immune responses induced by IFN-α in treatment-naïve, HCV-infected patients, focusing on the differentiation of dendritic cells (DC), the central regulators of both innate and adaptive immunity, from blood monocytes (MO), the major precursors of DC.

Methods:  A group of patients (n > 10) with chronic HCV infection, who had not received any treatment for the infection, were recruited. Heparinized and coagulated blood samples were collected right before the first IFN-α injection (without ribavirin) and at ~20 hours post-injection, after which the patients were given ribavirin. Freshly isolated MO were analyzed for their phenotypes and functions, and sera were used for cytokine assays and MO culture. 

Results:  Twenty hours after IFN-α treatment, a large proportion of MO exhibited downregulation of macrophage-associated surface markers, enhanced expression of costimultory and adhesion molecules and induced expression of several DC-restricted surface markers, indicating MO-to-DC differentiation. These DC-like MO were able to migrate towards tissue-derived chemokines and a large proportion of them underwent activation-induced cell death (AICD) in vivo. IFN-α treatment also markedly increased the proportion of CD16+ MO, the immediate DC precursors. Finally, the MO-to-DC differentiation appears to be mediated by IFN-α-induced serum factors, but not IFN-α per se

Conclusion:  IFN-α treatment triggers rapid and sizable differentiation of DCs from MO in HCV-infected patients. Further studies will investigate whether the variability in IFN-α-induced MO-to-DC differentiation and AICD correlates with the effectiveness of therapy and can be used as an early predictor for treatment outcome.

Yun-Chi Chen, PhD, Biology, Morgan State University, Baltimore, MD and Kjell J. Wiberg, MD, Infectious Diseases, Chase Brexton Health Services, Baltimore, MD

Disclosures:

Y. C. Chen, None

K. J. Wiberg, None

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