Involvement of chemokine receptor CXCR3 in the defense mechanism against Neospora caninum infection in C57BL/6 mice.
Involvement of chemokine receptor CXCR3 in the defense mechanism against Neospora caninum infection in C57BL/6 mice.
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DOI：
10.3389/fmicb.2022.1045106
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发表时间：
2022
影响因子：
5.2
通讯作者：
Nishikawa, Yoshifumi
中科院分区：
文献类型：
--
作者：
Abdelbaky, Hanan H.;Mitsuhashi, Shuichiro;Watanabe, Kenichi;Ushio, Nanako;Miyakawa, Miku;Furuoka, Hidefumi;Nishikawa, Yoshifumi
C-X-C基序趋化因子受体3（CXCR 3）是控制白细胞迁移的重要受体，但其在犬新孢子虫感染中的作用尚未见报道。在此，我们研究了CXCR 3在耐氮机制中的相关性。犬感染小鼠。所有实验均使用野生型（WT）C57 BL/6小鼠和CXCR 3敲除（CXCR 3 KO）小鼠。WT小鼠表现出很高的存活率（100%），而80%的CXCR 3 KO小鼠死于N.犬感染50天内。与WT小鼠相比，CXCR 3 KO小鼠在感染的亚急性期表现出显著更低的体重和更高的临床评分。流式细胞术分析显示，在感染后5天（dpi），与WT小鼠相比，CXCR 3 KO小鼠具有显著增加的CD 11 c阳性细胞的比例和数量。然而，血清和腹水中的IL-6和IFN-γ水平在5 dpi时在所有组中相似。此外，在5和21 dpi时，在CXCR 3 KO和WT小鼠的脑、脾、肺或肝组织中未检测到寄生虫负荷的差异。从感染后30天的小鼠收集的脑组织的mRNA分析显示，炎症反应基因的表达水平没有变化。然而，与WT小鼠相比，感染CXCR 3 KO小鼠的脑组织在21 dpi时显示出显著的坏死和小胶质细胞活化。有趣的是，在30 dpi时，与WT小鼠的脑组织相比，CXCR 3 KO小鼠的脑组织显示出显著更低数量的FoxP 3+细胞。因此，我们的研究表明，感染CXCR 3 KO小鼠的脑组织中缺乏活性调节性T细胞是这些小鼠与WT小鼠相比具有严重坏死和较低存活率的主要原因。因此，CXCR 3+调节性T细胞可能在控制新孢子虫病中发挥关键作用。
C-X-C motif chemokine receptor 3 (CXCR3) is an important receptor controlling the migration of leukocytes, although there is no report regarding its role in Neospora caninum infection. Herein, we investigated the relevance of CXCR3 in the resistance mechanism to N. caninum infection in mice. Wild-type (WT) C57BL/6 mice and CXCR3-knockout (CXCR3KO) mice were used in all experiments. WT mice displayed a high survival rate (100%), while 80% of CXCR3KO mice succumbed to N. caninum infection within 50 days. Compared with WT mice, CXCR3KO mice exhibited significantly lower body weights and higher clinical scores at the subacute stage of infection. Flow cytometric analysis revealed CXCR3KO mice as having significantly increased proportions and numbers of CD11c-positive cells compared with WT mice at 5 days post infection (dpi). However, levels of interleukin-6 and interferon-γ in serum and ascites were similar in all groups at 5 dpi. Furthermore, no differences in parasite load were detected in brain, spleen, lungs or liver tissue of CXCR3KO and WT mice at 5 and 21 dpi. mRNA analysis of brain tissue collected from infected mice at 30 dpi revealed no changes in expression levels of inflammatory response genes. Nevertheless, the brain tissue of infected CXCR3KO mice displayed significant necrosis and microglial activation compared with that of WT mice at 21 dpi. Interestingly, the brain tissue of CXCR3KO mice displayed significantly lower numbers of FoxP3+ cells compared with the brain tissue of WT mice at 30 dpi. Accordingly, our study suggests that the lack of active regulatory T cells in brain tissue of infected CXCR3KO mice is the main cause of these mice having severe necrosis and lower survival compared with WT mice. Thus, CXCR3+ regulatory T cells may play a crucial role in control of neosporosis.
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影响因子：
4.4
作者：
Christensen, Jeanette Erbo;de Lemos, Carina;Thomsen, Allan Randrup
通讯作者：
Thomsen, Allan Randrup
DOI：
10.1073/pnas.87.14.5238
发表时间：
1990-07-01
影响因子：
11.1
作者：
FARBER, JM
通讯作者：
FARBER, JM
影响因子：
4.4
作者：
de Lemos, C;Christensen, JE;Thomsen, AR
通讯作者：
Thomsen, AR
影响因子：
4.4
作者：
Hansen, Diana S.;Bernard, Nicholas J.;Schofield, Louis
通讯作者：
Schofield, Louis
DOI：
10.1084/jem.187.12.2009
发表时间：
1998-06-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cole KE;Strick CA;Paradis TJ;Ogborne KT;Loetscher M;Gladue RP;Lin W;Boyd JG;Moser B;Wood DE;Sahagan BG;Neote K
通讯作者：
Neote K