CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes.
CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes.
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作者：
Kim JH;Patil AM;Choi JY;Kim SB;Uyangaa E;Hossain FM;Park SY;Lee JH;Kim K;Eo SK
日本脑炎病毒(JEV)是一种重新出现的人畜共患黄病毒，由于气候和人口结构的快速变化，它对全球的健康和福利构成越来越大的威胁。尽管CCR2-CCL2轴在CD11b+Ly-6CHI单核细胞转运中发挥重要作用，以调节免疫病理疾病，但在乙脑病毒感染所致的病毒性脑炎中，CCR2-CCL2轴在单核细胞转运中的作用知之甚少。在这里，我们利用CCR2和CCL2消融的小鼠模型，探讨了CCR2及其配体CCL2在乙脑病毒感染引起的乙脑中的作用。有些令人惊讶的是，CCR2和CCL2的消融导致了截然不同的乙脑易感性。CCR2消融诱导了对乙脑的抗性增强，而CCL2消融则显著增加了对乙脑的敏感性。CCR2和CCL2对JE进展的这种对比调节与Ly-6chi单核细胞和Ly-6Ghi粒细胞的中枢神经系统(CNS)浸润有关。CCL2消融的小鼠中枢神经系统中CC和CXC趋化因子的表达也增强，这似乎诱导了CNS对这些细胞群的渗透。然而，我们的数据显示，CCR2和CCL2消融小鼠对乙脑的不同调节不太可能是由天生的自然杀伤细胞和适应性T细胞反应介导的。此外，在感染的骨髓嵌合模型中，造血干细胞来源的白细胞产生的CCL2在Ly-6chi单核细胞的中枢神经系统积聚中起主导作用，从而加剧乙脑的进展。总之，我们的数据表明，CCL2在提供对乙脑病毒感染引起的乙脑的保护方面发挥了重要作用。此外，阻断CCR2，而不是CCL2，将有助于乙脑预防和治疗策略的制定。
Japanese encephalitis virus (JEV) is a re‐emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2–CCL2 axis plays an important role in trafficking CD11b+ Ly‐6Chi monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2‐ and CCL2‐ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly‐6Chi monocytes and Ly‐6Ghi granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2‐ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2‐ and CCL2‐ablated mice was unlikely to be mediated by innate natural killer and adaptive T‐cell responses. Furthermore, CCL2 produced by haematopoietic stem cell‐derived leucocytes played a dominant role in CNS accumulation of Ly‐6Chi monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE.
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LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
影响因子：
3.8
作者：
Boivin, Nicolas;Menasria, Rafik;Boivin, Guy
通讯作者：
Boivin, Guy
影响因子：
14.8
作者：
Chattopadhyay, Pratip K.;Yu, Joanne;Roederer, Mario
通讯作者：
Roederer, Mario
影响因子：
7.3
作者：
Ariel A;Serhan CN
通讯作者：
Serhan CN
影响因子：
3.8
作者：
Chen, Chun-Jung;Ou, Yen-Chuan;Chen, Jian-Hong
通讯作者：
Chen, Jian-Hong