期刊
JOURNAL OF NEUROINFLAMMATION
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12974-016-0655-y
关键词
Pneumococcal meningitis; Pneumolysin; Live cell imaging; Streptococcus pneumoniae; Zebrafish; Host-microbe interaction
资金
- Netherlands Organization for Health Research and Development (ZonMw
- NWO-Veni grant) [2012 [916.13.078]]
- Netherlands Organization for Health Research and Development (ZonMw
- NWO-Vidi grant) [2010 [016.116.358]]
- European Research Council (ERC Starting Grant) [281156]
Background: Streptococcus pneumoniae is one of the most important causes of bacterial meningitis, an infection where unfavourable outcome is driven by bacterial and host-derived toxins. In this study, we developed and characterized a pneumococcal meningitis model in zebrafish embryos that allows for real-time investigation of early host-microbe interaction. Methods: Zebrafish embryos were infected in the caudal vein or hindbrain ventricle with green fluorescent wild-type 5. pneumoniae D39 or a pneumolysin-deficient mutant. The kdrl:mCherry transgenic zebrafish line was used to visualize the blood vessels, whereas phagocytic cells were visualized by staining with far red anti-L-plastin or in mpx:GFP/mpeg1:mCherry zebrafish, that have green fluorescent neutrophils and red fluorescent macrophages. Imaging was performed by fluorescence confocal and time-lapse microscopy. Results: After infection by caudal vein, we saw focal clogging of the pneumococci in the blood vessels and migration of bacteria through the blood-brain barrier into the subarachnoid space and brain tissue. Infection with pneumolysin-deficient S. pneumoniae in the hindbrain ventricle showed attenuated growth and migration through the brain as compared to the wild-type strain. Time-lapse and confocal imaging revealed that the initial innate immune response to 5. pneumonie in the subarachnoid space mainly consisted of neutrophils and that pneumolysin-mediated cytolytic activity caused a marked reduction of phagocytes. Conclusions: This new meningitis model permits detailed analysis and visualization of host-microbe interaction in pneumococcal meningitis in real time and is a very promising tool to further our insights in the pathogenesis of pneumococcal meningitis.
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