CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses.
CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses.
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DOI：
10.3390/v12111252
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发表时间：
2020-11-02
期刊：
影响因子：
--
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Lin T;Geng T;Harrison AG;Yang D;Vella AT;Fikrig E;Wang P
新兴和再发的致关节炎甲病毒，如基孔肯雅病毒（CHIKV）和奥-奈氏病毒，会引发与炎症免疫反应相关的急性和慢性致残性关节痛。大约50%的基孔肯雅病毒感染患者会出现持续6个月至数年的风湿症状。然而，单个免疫信号通路在甲病毒关节炎发病机制中的生理功能仍知之甚少。在此，我们报道趋化因子CXCL10（对单核细胞/巨噬细胞/T细胞有趋化作用）的缺乏会导致与野生型动物相同的病毒血症，但在关节炎疾病高峰期（感染后6 - 8天）足垫中的免疫浸润较少且病毒载量较低。感染后巨噬细胞是足垫中最大的免疫细胞群，在Cxcl10 - / - 小鼠中显著减少。与野生型小鼠相比，Cxcl10 - / - 小鼠中性粒细胞和巨噬细胞中的病毒RNA载量降低。总之，我们的研究结果表明CXCL10信号促进了甲病毒疾病的发病机制，并提示CXCL10可能是缓解甲病毒关节炎的一个治疗靶点。
Emerging and re-emerging arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and O’nyong nyong virus, cause acute and chronic crippling arthralgia associated with inflammatory immune responses. Approximately 50% of CHIKV-infected patients suffer from rheumatic manifestations that last 6 months to years. However, the physiological functions of individual immune signaling pathways in the pathogenesis of alphaviral arthritis remain poorly understood. Here, we report that a deficiency in CXCL10, which is a chemoattractant for monocytes/macrophages/T cells, led to the same viremia as wild-type animals, but fewer immune infiltrates and lower viral loads in footpads at the peak of arthritic disease (6–8 days post infection). Macrophages constituted the largest immune cell population in footpads following infection, and were significantly reduced in Cxcl10−/− mice. The viral RNA loads in neutrophils and macrophages were reduced in Cxcl10−/− compared to wild-type mice. In summary, our results demonstrate that CXCL10 signaling promotes the pathogenesis of alphaviral disease and suggest that CXCL10 may be a therapeutic target for mitigating alphaviral arthritis.
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DOI：
10.1084/jem.20070962
发表时间：
2008-01-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pal U;Wang P;Bao F;Yang X;Samanta S;Schoen R;Wormser GP;Schwartz I;Fikrig E
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DOI：
10.1084/jem.182.1.155
发表时间：
1995-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Tosato G