The chemokine receptor CCR5, a therapeutic target for HIV/AIDS antagonists, is critical for recovery in a mouse model of Japanese encephalitis.
The chemokine receptor CCR5, a therapeutic target for HIV/AIDS antagonists, is critical for recovery in a mouse model of Japanese encephalitis.
复制标题
DOI：
10.1371/journal.pone.0044834
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lobigs M
中科院分区：
文献类型：
--
作者：
Larena M;Regner M;Lobigs M
日本脑炎是由蚊媒黄病毒引起的严重中枢神经系统（CNS）炎症性疾病。在目前的研究中，我们研究了缺乏趋化因子受体CCR5表达的小鼠对JEV的免疫应答，CCR5在感染过程中激活和趋化白细胞。我们表明，CCR5作为一个主机抗病毒因子对日本脑炎，与CCR5缺陷显着增加死亡率，并在中枢神经系统中的病毒负荷。体液免疫反应，这是必不可少的恢复从JEV感染，是相似的幅度在CCR 5充足和缺陷小鼠。然而，CCR5的缺乏导致细胞免疫应答的多方面缺陷，其特征在于自然杀伤细胞和CD8+ T细胞活性降低、脾细胞构成低以及白细胞向脑的运输受损。有趣的是，过继转移免疫脾细胞，耗尽B淋巴细胞，增加了CCR 5缺陷受体小鼠对JEV的抵抗力，无论细胞是从CCR 5缺陷或野生型供体小鼠获得的，并且仅当在攻击后1天而不是3天转移时。这一结果与CCR5表达增强淋巴细胞活化从而促进日本脑炎宿主存活的机制一致。
Japanese encephalitis is a severe central nervous system (CNS) inflammatory disease caused by the mosquito-borne flavivirus, Japanese encephalitis virus (JEV). In the current study we have investigated the immune responses against JEV in mice lacking expression of the chemokine receptor CCR5, which functions in activation and chemotaxis of leukocytes during infection. We show that CCR5 serves as a host antiviral factor against Japanese encephalitis, with CCR5 deficiency markedly increasing mortality, and viral burden in the CNS. Humoral immune responses, which are essential in recovery from JEV infection, were of similar magnitude in CCR5 sufficient and deficient mice. However, absence of CCR5 resulted in a multifaceted deficiency of cellular immune responses characterized by reduced natural killer and CD8+ T cell activity, low splenic cellularity, and impaired trafficking of leukocytes to the brain. Interestingly, adoptive transfer of immune spleen cells, depleted of B lymphocytes, increased resistance of CCR5-deficient recipient mice against JEV regardless of whether the cells were obtained from CCR5-deficient or wild-type donor mice, and only when transferred at one but not at three days post-challenge. This result is consistent with a mechanism by which CCR5 expression enhances lymphocyte activation and thereby promotes host survival in Japanese encephalitis.
登录
查看更多内容
DOI：
10.1084/jem.20102110
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kohlmeier JE;Reiley WW;Perona-Wright G;Freeman ML;Yager EJ;Connor LM;Brincks EL;Cookenham T;Roberts AD;Burkum CE;Sell S;Winslow GM;Blackman MA;Mohrs M;Woodland DL
通讯作者：
Woodland DL
影响因子：
30.5
作者：
Hugues, Stephanie;Scholer, Alix;Fetler, Luc
通讯作者：
Fetler, Luc
影响因子：
3.8
作者：
KING, NJC;KESSON, AM
通讯作者：
KESSON, AM
影响因子：
5.4
作者：
Fadell, Shaza A.;Bromley, Shannon K.;Medoff, Benjamin D.;Luster, Andrew D.
通讯作者：
Luster, Andrew D.
影响因子：
3.7
作者：
Colombage, G;Hall, R;Lobigs, M
通讯作者：
Lobigs, M