Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and higher mortality in mice with of pneumococcal meningitis
Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and higher mortality in mice with of pneumococcal meningitis
复制标题
DOI：
10.1111/imm.12324
复制
发表时间：
2014-11-01
期刊：
影响因子：
6.4
通讯作者：
Brandenburg, Lars-Ove
中科院分区：
文献类型：
--
作者：
Oldekamp, Sandra;Pscheidl, Sebastian;Brandenburg, Lars-Ove
细菌性脑膜炎，尽管在研究和新的治疗策略的发展，仍然是一个严重的神经后遗症的原因。大脑受到血脑屏障和先天免疫系统的保护，免受病原体的渗透。入侵的病原体被模式识别受体识别，包括由中枢神经系统的免疫细胞表达的G蛋白偶联甲酰基肽受体（FPRs）。细菌性脑膜炎期间FPRs的表达上调，但对炎症进展的后果和对死亡率的影响还远未明确。因此，我们使用mFPR 1和mFPR 2缺陷小鼠来研究对肺炎球菌脑膜炎小鼠模型中的炎症、细菌生长和死亡率的影响。我们的研究结果显示，与野生型小鼠相比，mFPR1/2缺陷小鼠的细菌负荷增加，中性粒细胞浸润增加，死亡率较高。mFPR1或mFPR2缺陷小鼠的神经胶质细胞密度也显著增加，而细菌性脑膜炎的免疫反应，包括抗炎细胞因子和抗菌肽的表达下降。总之，结果表明，FPR 1和FPR 2在中枢神经系统内对肺炎链球菌的先天免疫应答中起重要作用，并且与野生型小鼠相比，缺乏受体导致炎症应答失调。
Bacterial meningitis is, despite progress in research and the development of new treatment strategies, still a cause of severe neuronal sequelae. The brain is protected from penetrating pathogens by both the blood-brain barrier and the innate immune system. The invading pathogens are recognized by pattern recognition receptors including the G-protein coupled formyl peptide receptors (FPRs), which are expressed by immune cells of the central nervous system. The expression of FPRs is up-regulated during bacterial meningitis, but the consequence on the progression of inflammation and impact on mortality are far from clear. Therefore, we used mFPR1 and mFPR2-deficient mice to investigate the effects on inflammation, bacterial growth and mortality in a mouse model of pneumococcal meningitis. Our results revealed increased bacterial burden, increased neutrophil infiltration and higher mortality in mFPR1/2-deficient mice in comparison to wild-type mice. The mFPR1- or mFPR2-deficient mice also showed significantly increased glial cell density, whereas the immune responses including the expression of anti-inflammatory cytokines and antimicrobial peptides were decreased in bacterial meningitis. Taken together, the results suggest that FPR1 and FPR2 play an important role in the innate immune responses against Streptococcus pneumoniae within the central nervous system and the lack of the receptors leads to a dysregulation of the inflammatory response compared with wild-type mice.