Umeda Kousuke, Goto Youta, Watanabe Kenichi, Ushio Nanako, Fereig Ragab M, Ihara Fumiaki, Tanaka Sachi, Suzuki Yutaka, Nishikawa Yoshifumi
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Hokkaido, Japan.
Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Hokkaido, Japan.
Microorganisms. 2021 Nov 12;9(11):2340. doi: 10.3390/microorganisms9112340.
The obligate intracellular parasite infects warm-blooded animals, including humans. We previously revealed through a whole-brain transcriptome analysis that infection with in mice causes immune response-associated genes to be upregulated, for instance, chemokines and chemokine receptors such as CXC chemokine receptor 3 (CXCR3) and its ligand CXC chemokine ligand 10 (CXCL10). Here, we describe the effect of CXCR3 on responses against infection in the mouse brain. In vivo assays using CXCR3-deficient mice showed that the absence of CXCR3 delayed the normal recovery of body weight and increased the brain parasite burden, suggesting that CXCR3 plays a role in the control of pathology in the brain, the site where chronic infection occurs. Therefore, to further analyze the function of CXCR3 in the brain, we profiled the gene expression patterns of primary astrocytes and microglia by RNA sequencing and subsequent analyses. CXCR3 deficiency impaired the normal upregulation of immune-related genes during infection, in astrocytes and microglia alike. Collectively, our results suggest that the immune-related genes upregulated by CXCR3 perform a particular role in controlling pathology when the host is chronically infected with in the brain.
这种专性细胞内寄生虫会感染包括人类在内的温血动物。我们之前通过全脑转录组分析揭示，小鼠感染该寄生虫会导致免疫反应相关基因上调，例如趋化因子和趋化因子受体，如CXC趋化因子受体3（CXCR3）及其配体CXC趋化因子配体10（CXCL10）。在此，我们描述了CXCR3对小鼠脑部针对该寄生虫感染的反应的影响。使用CXCR3缺陷小鼠进行的体内实验表明，缺乏CXCR3会延迟体重的正常恢复，并增加脑部寄生虫负荷，这表明CXCR3在控制慢性感染发生部位——大脑的病理过程中发挥作用。因此，为了进一步分析CXCR3在大脑中的功能，我们通过RNA测序及后续分析对原代星形胶质细胞和小胶质细胞的基因表达模式进行了分析。CXCR3缺陷会损害感染期间星形胶质细胞和小胶质细胞中免疫相关基因的正常上调。总体而言，我们的结果表明，当宿主大脑长期感染该寄生虫时，由CXCR3上调的免疫相关基因在控制病理过程中发挥着特殊作用。
