Ribavirin enhances myeloid-derived suppressor cell differentiation through CXCL9/10 downregulation

Abstract

Elevation of myeloid-derived suppressor cells (MDSCs) was observed in some viral infectious diseases. In this study, we studied whether ribavirin, a widely used clinical antiviral drug, could impact the differentiation of human MDSCs in vitro. Flow cytometric analysis showed that ribavirin treatment (5–20 µg/ml) significantly enhanced the differentiation of monocytic MDSCs in a dose-dependent manner. The ribavirin-generated MDSCs were immune-suppressive toward autologous T cells. The mRNA expression of some cytokines was further examined by quantitative reverse transcription polymerase chain reaction. We observed a significant down-regulation of chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 mRNA in ribavirin-generated MDSCs, when compared with control. Peripheral blood mononuclear cells from clinical chronic hepatitis C patients subjected to ribavirin therapy also displayed a similar suppression in CXCL9/10 mRNA expression. Administration of recombinant CXCL9/10 proteins clearly counteracted the effect of ribavirin on MDSCs. In summary, this study showed that ribavirin enhanced human MDSCs differentiation in vitro, which may be attribute to the down-regulation of CXCL9/10 expression.

• Chemokine (C-X-C motif) ligand
• myeloid-derived suppressor cells
• ribavirin

Supplementary material available online

Supplementary Table 1 and Supplementary Figures 1–4.