| Real-time imaging of trapping and urease-dependent transmigration of cryptococcus neoformans in mouse brain | |
| Shi, Meiqing1; Li, Shu Shun1; Zheng, Chunfu2; Jones, Gareth J.1; Kim, Kwang Sik3; Zhou, Hong4; Kubes, Paul4; Mody, Christopher H.1,5 | |
| 刊名 | Journal of clinical investigation
 |
| 2010-05-01 | |
| 卷号 | 120期号:5页码:1683-1693 |
| ISSN号 | 0021-9738 |
| DOI | 10.1172/jci41963 |
| 通讯作者 | Mody, christopher h.(cmody@ucalgary.ca) |
| 英文摘要 | Infectious meningitis and encephalitis is caused by invasion of circulating pathogens into the brain. it is unknown how the circulating pathogens dynamically interact with brain endothelium under shear stress, leading to invasion into the brain. here, using intravital microscopy, we have shown that cryptococcus neoformans, a yeast pathogen that causes meningoencephalitis, stops suddenly in mouse brain capillaries of a similar or smaller diameter than the organism, in the same manner and with the same kinetics as polystyrene microspheres, without rolling and tethering to the endothelial surface. trapping of the yeast pathogen in the mouse brain was not affected by viability or known virulence factors. after stopping in the brain, c. neoformans was seen to cross the capillary wall in real time. in contrast to trapping, viability, but not replication, was essential for the organism to cross the brain microvasculature. using a knockout strain of c. neoformans, we demonstrated that transmigration into the mouse brain is urease dependent. to determine whether this could be amenable to therapy, we used the urease inhibitor flurofamide. flurofamide ameliorated infection of the mouse brain by reducing transmigration into the brain. together, these results suggest that c. neoformans is mechanically trapped in the brain capillary, which may not be amenable to pharmacotherapy, but actively transmigrates to the brain parenchyma with contributions from urease, suggesting that a therapeutic strategy aimed at inhibiting this enzyme could help prevent meningitis and encephalitis caused by c. neoformans infection. |
| WOS关键词 | MICROVASCULAR ENDOTHELIAL-CELLS ; CENTRAL-NERVOUS-SYSTEM ; VAR. GRUBII SEROTYPE ; LEUKOCYTE RECRUITMENT ; MURINE MODEL ; P-SELECTIN ; IN-VITRO ; BARRIER ; BLOOD ; INVASION |
| WOS研究方向 | Research & Experimental Medicine |
| WOS类目 | Medicine, Research & Experimental |
| 语种 | 英语 |
| 出版者 | AMER SOC CLINICAL INVESTIGATION INC |
| WOS记录号 | WOS:000277248000034 |
| 内容类型 | 期刊论文 |
| URI标识 | http://www.corc.org.cn/handle/1471x/2375710 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Mody, Christopher H. |
| 作者单位 | 1.Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada 2.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Peoples R China 3.Johns Hopkins Univ, Sch Med, Div Pediat Infect Dis, Baltimore, MD USA 4.Univ Calgary, Dept Physiol & Biophys, Calgary, AB T2N 4N1, Canada 5.Univ Calgary, Dept Internal Med, Calgary, AB T2N 4N1, Canada |
| 推荐引用方式 GB/T 7714 | Shi, Meiqing,Li, Shu Shun,Zheng, Chunfu,et al. Real-time imaging of trapping and urease-dependent transmigration of cryptococcus neoformans in mouse brain[J]. Journal of clinical investigation,2010,120(5):1683-1693. |
| APA | Shi, Meiqing.,Li, Shu Shun.,Zheng, Chunfu.,Jones, Gareth J..,Kim, Kwang Sik.,...&Mody, Christopher H..(2010).Real-time imaging of trapping and urease-dependent transmigration of cryptococcus neoformans in mouse brain.Journal of clinical investigation,120(5),1683-1693. |
| MLA | Shi, Meiqing,et al."Real-time imaging of trapping and urease-dependent transmigration of cryptococcus neoformans in mouse brain".Journal of clinical investigation 120.5(2010):1683-1693. |
| 个性服务 |
| 查看访问统计 |
| 相关权益政策 |
| 暂无数据 |
| 收藏/分享 |
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
修改评论