Ehlin-Henriksson Barbro, Liang Wu, Cagigi Alberto, Mowafi Frida, Klein George, Nilsson Anna
Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Immunology. 2009 Aug;127(4):549-57. doi: 10.1111/j.1365-2567.2008.03029.x.
Chemokines and chemokine receptors are likely to play important roles in the pathogenesis of Epstein-Barr virus (EBV) -associated disease. The primary EBV infection occurs in the oropharynx where the virus infects mainly tonsillar B cells. We have previously shown that CXCR4 expression on tonsillar B cells is modulated by EBV. Here, CXCR5 and CCR7 expression, which is important for migration into lymphoid tissue, was followed for 14 days after EBV infection of tonsillar B cells. Early after infection (2 days) there were only minor changes in CXCR5 and CCR7 expression. However, at day 7 the expression of CXCR5, as well as of CCR7, was decreased and by day 14 these molecules were no longer present at the cell surface. Furthermore, EBV infection affects the chemotactic response to CXCL13 and CCL21 (the ligands for CXCR5 and CCR7, respectively) with a reduction of ligand-induced migration at day 2. Using gene expression profiling, we identified an additional set of chemokines and chemokine receptors that were changed upon EBV infection in comparison with non-infected tonsillar B cells. In particular, messenger RNA expression for CCR9 and the complement receptor C5AR1 was increased. Both receptors mediate homing to mucosal tissue. The alterations of the expression of these molecules may lead to retention of EBV-infected tonsillar B cells in the interfollicular region of the tonsil.
趋化因子和趋化因子受体可能在爱泼斯坦-巴尔病毒（EBV）相关疾病的发病机制中发挥重要作用。原发性EBV感染发生在口咽，病毒主要感染扁桃体B细胞。我们之前已经表明，EBV可调节扁桃体B细胞上CXCR4的表达。在此，在扁桃体B细胞感染EBV后14天，追踪了对迁移到淋巴组织很重要的CXCR5和CCR7的表达情况。感染后早期（2天），CXCR5和CCR7的表达仅有轻微变化。然而，在第7天，CXCR5以及CCR7的表达降低，到第14天这些分子不再出现在细胞表面。此外，EBV感染影响对CXCL13和CCL21（分别为CXCR5和CCR7的配体）的趋化反应，在第2天配体诱导的迁移减少。利用基因表达谱分析，我们鉴定出一组与未感染的扁桃体B细胞相比，在EBV感染后发生变化的趋化因子和趋化因子受体。特别是，CCR9和补体受体C5AR1的信使核糖核酸表达增加。这两种受体都介导归巢至黏膜组织。这些分子表达的改变可能导致EBV感染的扁桃体B细胞滞留在扁桃体的滤泡间区域。
