在慢性HBV感染患者, 浆细胞树突状细胞功能改变和自然杀伤细

StephenW

http://www.gastrojournal.org/article/S0016-5085%2812%2901305-4/abstract
Altered Functions of Plasmacytoid Dendritic Cells and Reduced Cytolytic Activity of Natural Killer Cells in Patients With Chronic HBV Infection
在慢性HBV感染患者, 浆细胞树突状细胞功能改变和自然杀伤细胞的杀伤活性降低


    Jeremie Martinet    ,    Tania Dufeu–Duchesne    ,    Juliana Bruder Costa    ,
    Sylvie Larrat    ,    Alice Marlu    ,    Vincent Leroy    ,    Joel Plumas    ,
    Caroline Aspord

Received 27 February 2012; accepted 29 August 2012. published online 10 September 2012.

  
Background & Aims

Hepatitis B virus (HBV) modulates the immune system to escape clearance. Plasmacytoid dendritic cells (pDCs) initiate antiviral immunity and might determine outcomes of HBV infections. Functional defects in pDCs and natural killer (NK) cells have been reported in patients with chronic HBV infection. However, the mechanisms of these immune dysfunctions and the interactions between pDCs and NK cells have not been determined. We investigated features of pDCs from patients with chronic HBV infection and their interactions with NK cells.
Methods

We used flow cytometry and cytokine assays to analyze pDCs from patients with chronic HBV infection (118 aviremic and 67 viremic) and compared them with pDCs from uninfected individuals (controls). We performed coculture assays to analyze the ability of pDCs to activate heterologous NK cells.
Results

Circulating and hepatic pDCs from patients with chronic HBV infection had higher levels of activation than pDCs from controls and defective responses to stimulation with Toll-like receptor 9 ligand (TLR9-L), regardless of the patient's viral load. TLR9-L–activated pDCs from viremic patients with HBV did not induce cytolytic activity of NK cells. This altered function of pDCs was associated with reduced expression of OX40L and could be reproduced by incubating control pDCs with plasma from viremic patients with HBV. A high level of interferon-induced protein 10 (IP-10 or CXCL10) and hepatitis B surface and e antigens might induce these defective pDC functions.
Conclusions

HBV escapes antiviral immunity by altering pDC functions, to disrupt interactions between pDC and NK cells. This could reduce immune control of HBV and lead to chronic infection.

StephenW

背景与目的

乙型肝炎病毒（HBV）调节免疫系统，以逃避间隙。浆细胞样树突状细胞（PDC）的启动抗病毒免疫，并可能决定HBV感染的结果。据报道，在慢性HBV感染患者在PDC和自然杀伤（NK）细胞的功能缺陷。然而，这些免疫功能障碍的pDCs和NK细胞之间的相互作用中的机制尚未确定。我们功能的pDCs从患者的慢性HBV感染与NK细胞和它们之间的相互作用。
方法

我们用流式细胞仪和细胞因子的检测从患者的慢性HBV感染（为118 aviremic和67个病毒血症）和他们的pDCs未感染的人（对照组）进行比较分析的pDCs。我们进行共培养实验分析的pDCs激活异源NK细胞的能力。
结果

循环和肝脏的pDCs从慢性HBV感染患者有较高的激活水平比PDC上控制和有缺陷的反应与Toll样受体配体（TLR9-L）的刺激，无论患者的病毒载量。 TLR9-L-活化的pDCs从HBV病毒血症患者没有诱导NK细胞的细胞溶解活性。此功能改变的pDCs与OX40L的表达降低，可以由孵化控制PDCS与HBV病毒血症患者血浆转载。高水平的干扰素诱导蛋白10（IP-10或CXCL10）和乙肝表面抗原（HBsAg）和e抗原可能会导致这些有缺陷的PDC功能。
结论

HBV逃避抗病毒免疫通过改变pDC的功能，破坏PDC和NK细胞之间的相互作用。这样可以减少HBV慢性感染导致的免疫控制。