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首页> 外文期刊>Infection and immunity >Induction of the Antimicrobial Peptide CRAMP in the Blood-Brain Barrier and Meninges after Meningococcal Infection
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Induction of the Antimicrobial Peptide CRAMP in the Blood-Brain Barrier and Meninges after Meningococcal Infection

机译：脑膜炎球菌感染后血脑屏障和脑膜中抗菌肽CRAMP的诱导

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摘要

Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP.
机译：抗菌肽存在于大多数生物物种中，并构成先天免疫的重要效应分子。最近，我们和其他人已经在大脑中检测到抗菌肽。这是一个很少感染的器官，主要归因于血脑屏障（BBB）和脑膜的保护功能。由于尚不清楚BBB和脑膜的杀菌特性，因此我们假设抗菌肽可能在这些屏障中起作用。我们通过用神经致病性脑膜炎奈瑟氏球菌（Neisseria meningitidis）感染小鼠来解决这个假设。通过免疫组织化学结合共聚焦显微镜分析脑中抗微生物肽CRAMP的表达。感染后，我们在BBB的内皮细胞和脑膜细胞中观察到了CRAMP的诱导。为了探索CRAMP在脑膜炎球菌疾病中的功能，我们感染了缺少CRAMP基因的小鼠。尽管CRAMP似乎不能保护脑部免受脑膜炎球菌的侵袭，但CRAMP敲除小鼠比野生型小鼠更容易受到脑膜炎球菌感染，并表现出血液，肝脏和脾脏中脑膜炎球菌的增长。此外，我们可以证明碳酸盐（一种在代谢性酸中毒期间在循环中积累的化合物）使脑膜炎球菌更容易受到CRAMP的影响。

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