Hepatitis C lipo-Viro-particle from chronically infected patients interferes with TLR4 signaling in dendritic cell

慢性感染患者的丙型肝炎脂质病毒颗粒会干扰树突状细胞中的 TLR4 信号传导

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作者:Sophie Agaugué, Laure Perrin-Cocon, Patrice André, Vincent Lotteau

Background

Hepatitis C virus (HCV) can be purified from serum of chronically-infected patients in the form of Lipo-Viro-Particles (LVP), which are triglycerid-rich lipoprotein-like particles containing viral RNA and proteins. Since LVP is a constant feature of chronically infected patients, we asked whether purified LVP could interfere with the immune response by acting directly on dendritic cell (DC) function.

Conclusions

LVP can interfere with TLR4-triggered maturation of DC, inducing a shift in DC function that stimulates Th2 cells instead of Th1, by a mechanism that is ERK- and p38-MAPK-dependent. The effect of LVP on DC polarization was reversed by IFNalpha, providing an additional rationale for the interferon therapy of chronically-infected patients. By acting on TLR4 pathway with LVP, HCV may thus exploit a natural protective mechanism of the liver and the intestine normally used to control inflammation and immunity to commensal microorganisms.

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