CXCR3-deficiency protects influenza-infected CCR5-deficient mice from mortality.

CXCR3-deficiency protects influenza-infected CCR5-deficient mice from mortality.
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DOI:
10.1002/eji.200838628
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发表时间:
2008-12
影响因子:
5.4
通讯作者:
Luster, Andrew D.
Luster, Andrew D.
中科院分区:
医学3区
文献类型:
--
作者:
Fadell, Shaza A.;Bromley, Shannon K.;Medoff, Benjamin D.;Luster, Andrew D.

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缺乏趋化因子受体CCR5的小鼠容易死于正常的非致命性流感感染。在这里,我们发现CXCR3缺陷可以将CCR5缺陷小鼠从流感诱导的死亡中拯救出来。CCR5基因缺陷小鼠呼吸道单核巨噬细胞数量一过性增加,而CXCR3-CCR5双基因缺陷小鼠无明显变化。与野生型或CCR5缺陷的CD8效应细胞相比,抗原特异性的CXCR3-CCR5双缺陷CD8效应细胞进入呼吸道的效率较低。CXCR3-CCR5双缺陷感染小鼠炎性细胞浸润的减少与呼吸道中CCL2和干扰素γ的产生减少有关。最后,在一次病毒攻击中幸存下来的CXCR3-CCR5双缺陷小鼠免受致命的二次攻击,这表明缺乏这些趋化因子受体的小鼠的T细胞介导的保护性记忆没有受到损害。总之,CXCR3缺乏减弱了CCR5缺陷流感感染小鼠的致命性细胞免疫反应,而不会阻碍病毒清除或长期免疫。
Mice lacking the chemokine receptor CCR5 are susceptible to mortality from a normally non-lethal influenza infection. Here we found that CXCR3-deficiency rescued CCR5-deficient mice from influenza-induced mortality. The number of mononuclear phagocytes in the airways was transiently increased in CCR5-deficient mice but not in CXCR3-CCR5 double-deficient mice. Antigen-specific CXCR3-CCR5 double-deficient CD8 effector cells were less efficient at entering the airways compared to wild-type or CCR5-deficient CD8 effector cells. The decrease in inflammatory cell infiltrates in CXCR3-CCR5 double-deficient infected mice correlated with a decrease in CCL2 and IFNγ production in the airways. Finally, CXCR3-CCR5 double-deficient mice that survived the primary viral challenge were protected from a lethal secondary challenge, indicating that T cell-mediated protective memory was not compromised in mice lacking these chemokine receptors. In conclusion, CXCR3 deficiency attenuated the lethal cellular immune response in CCR5-deficient influenza-infected mice without hindering viral clearance or long-term immunity.
激活表型,而不是中心或效应子内存表型,可预测记忆CD8+ T细胞的回忆功效。
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