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肺炎球菌性脑膜炎患者及小鼠中CCL20及其受体CCR6对白细胞的吸引作用

Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis.

作者信息

Klein Matthias, Brouwer Matthijs C, Angele Barbara, Geldhoff Madelijn, Marquez Gabriel, Varona Rosa, Häcker Georg, Schmetzer Helga, Häcker Hans, Hammerschmidt Sven, van der Ende Arie, Pfister Hans-Walter, van de Beek Diederik, Koedel Uwe

机构信息

Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.

Department of Neurology, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.

出版信息

PLoS One. 2014 Apr 3;9(4):e93057. doi: 10.1371/journal.pone.0093057. eCollection 2014.

DOI:10.1371/journal.pone.0093057
PMID:24699535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3974727/
Abstract

We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.

摘要

我们之前将CCL20鉴定为肺炎球菌性脑膜炎患者脑脊液（CSF）中的一种早期趋化因子，但其功能相关性尚不清楚。在此，我们研究了CCL20及其受体CCR6在肺炎球菌性脑膜炎中的作用。在一项全国性前瞻性研究中，肺炎球菌性脑膜炎患者脑脊液中的CCL20水平显著升高，且与脑脊液白细胞计数相关。用抗CCL20抗体治疗的CCR6缺陷型肺炎球菌性脑膜炎小鼠和野生型肺炎球菌性脑膜炎小鼠的脑脊液白细胞计数均降低。脑脊液细胞增多症的减少还伴随着脑内细菌滴度的增加。额外的体外实验显示CCL20对粒细胞具有直接趋化活性。总之，我们的结果表明CCL20-CCR6轴是抵御肺炎球菌性脑膜炎的固有免疫防御的重要组成部分，可控制粒细胞募集。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/da7fa1502f39/pone.0093057.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/56c46aa493b6/pone.0093057.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/f55b5d75c033/pone.0093057.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/fb00843d349b/pone.0093057.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/7a070b9069bf/pone.0093057.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/da7fa1502f39/pone.0093057.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/56c46aa493b6/pone.0093057.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/3f6f7d61b817/pone.0093057.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/3ebf88dfce02/pone.0093057.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/f55b5d75c033/pone.0093057.g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/7a070b9069bf/pone.0093057.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcc/3974727/da7fa1502f39/pone.0093057.g007.jpg

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