Whiston Emily A, Sugi Norito, Kamradt Merideth C, Sack Coralynn, Heimer Susan R, Engelbert Michael, Wawrousek Eric F, Gilmore Michael S, Ksander Bruce R, Gregory Meredith S
The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
Infect Immun. 2008 Apr;76(4):1781-90. doi: 10.1128/IAI.01285-07. Epub 2008 Jan 28.
Bacterial infections of the eye highlight a dilemma that is central to all immune-privileged sites. On the one hand, immune privilege limits inflammation to prevent bystander destruction of normal tissue and loss of vision. On the other hand, bacterial infections require a robust inflammatory response for rapid clearance of the pathogen. We demonstrate that the retina handles this dilemma, in part, by activation of a protective heat shock protein. During Staphylococcus aureus-induced endophthalmitis, the small heat shock protein alphaB-crystallin is upregulated in the retina and prevents apoptosis during immune clearance of the bacteria. In the absence of alphaB-crystallin, mice display increased retinal apoptosis and retinal damage. We found that S. aureus produces a protease capable of cleaving alphaB-crystallin to a form that coincides with increased retinal apoptosis and tissue destruction. We conclude that alphaB-crystallin is important in protecting sensitive retinal tissue during destructive inflammation that occurs during bacterial endophthalmitis.
眼部细菌感染凸显了一个所有免疫赦免部位都存在的核心困境。一方面,免疫赦免限制炎症,以防止正常组织受到旁路途经的破坏以及视力丧失。另一方面,细菌感染需要强大的炎症反应来快速清除病原体。我们证明,视网膜部分地通过激活一种保护性热休克蛋白来应对这一困境。在金黄色葡萄球菌诱导的眼内炎期间,小热休克蛋白αB-晶体蛋白在视网膜中上调,并在细菌免疫清除过程中防止细胞凋亡。在缺乏αB-晶体蛋白的情况下,小鼠视网膜细胞凋亡增加且视网膜受损。我们发现金黄色葡萄球菌产生一种蛋白酶,能够将αB-晶体蛋白切割成一种与视网膜细胞凋亡增加和组织破坏相一致的形式。我们得出结论,αB-晶体蛋白在细菌性眼内炎期间发生的破坏性炎症过程中保护敏感的视网膜组织方面起着重要作用。