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黏膜佐剂霍乱毒素 B 对抗原非依赖性肺炎链球菌密度的限制作用。

Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B.

机构信息

Laboratory of Pediatric Infectious Diseases.

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen.

出版信息

J Infect Dis. 2016 Nov 15;214(10):1588-1596. doi: 10.1093/infdis/jiw160. Epub 2016 Apr 24.

Abstract

For many bacterial respiratory infections, development of (severe) disease is preceded by asymptomatic colonization of the upper airways. For Streptococcus pneumoniae, the transition to severe lower respiratory tract infection is associated with an increase in nasopharyngeal colonization density. Insight into how the mucosal immune system restricts colonization may provide new strategies to prevent clinical symptoms. Several studies have provided indirect evidence that the mucosal adjuvant cholera toxin subunit B (CTB) may confer nonspecific protection against respiratory infections. Here, we show that CTB reduces the pneumococcal load in the nasopharynx, which required activation of the caspase-1/11 inflammasome, mucosal T cells, and macrophages. Our findings suggest that CTB-dependent activation of the local innate response synergizes with noncognate T cells to restrict bacterial load. Our study not only provides insight into the immunological components required for containment and clearance of pneumococcal carriage, but also highlights an important yet often understudied aspect of adjuvants.

摘要

对于许多细菌性呼吸道感染,上呼吸道无症状定植是(严重)疾病发展的前兆。对于肺炎链球菌,下呼吸道感染向严重感染的转变与鼻咽定植密度的增加有关。了解黏膜免疫系统如何限制定植可能为预防临床症状提供新策略。几项研究提供了间接证据表明黏膜佐剂霍乱毒素亚单位 B(CTB)可能对呼吸道感染提供非特异性保护。在这里,我们表明 CTB 降低了鼻咽中的肺炎链球菌负荷,这需要半胱天冬酶-1/11 炎性体、黏膜 T 细胞和巨噬细胞的激活。我们的发现表明,CTB 依赖性激活局部先天反应与非同源 T 细胞协同作用以限制细菌负荷。我们的研究不仅深入了解了控制和清除肺炎球菌定植所需的免疫成分,还强调了佐剂一个重要但经常被研究不足的方面。

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