PDF(Pubmed)
Abstract：
The life-threatening disease streptococcal toxic shock-like syndrome (STSLS), caused by the bacterial pathogen Streptococcus suis (S. suis). Proinflammatory markers, bacterial load, granulocyte recruitment, and neutrophil extracellular traps (NETs) levels were monitored in wild-type (WT) and Fpr2-/- mice suffering from STSLS. LXA4 and AnxA1, anti-inflammatory mediators related to Fpr2, were used to identity a potential role of the Fpr2 in STSLS development. We also elucidated the function of Fpr2 at different infection sites by comparing the STSLS model with the S. suis-meningitis model. Compared with the WT mice, Fpr2-/- mice exhibited a reduced inflammatory response and bacterial load, and increased neutrophil recruitment. Pretreatment with AnxA1 or LXA4 impaired leukocyte recruitment and increased both bacterial load and inflammatory reactions in WT but not Fpr2-/- mice experiencing STSLS. These results indicated that Fpr2 impairs neutrophil recruitment during STSLS, and this impairment is enhanced by AnxA1 or LXA4. By comparing the functions of Fpr2 in different S. suis infection models, inflammation and NETs was found to hinder bacterial clearance in S. suis meningitis, and conversely accelerate bacterial clearance in STSLS. Therefore, interference with neutrophil recruitment could potentially be harnessed to develop new treatments for this infectious disease.
摘要：
威胁生命的疾病链球菌中毒性休克样综合征（STSLS），由细菌病原体猪链球菌(S.suis）。促炎标志物,细菌负荷，粒细胞招募,在患有STSLS的野生型(WT)和Fpr2-/-小鼠中监测嗜中性粒细胞胞外陷阱(NETs)水平。与Fpr2相关的抗炎介质LXA4和AnxA1用于鉴定Fpr2在STSLS发育中的潜在作用。我们还通过比较STSLS模型与猪链球菌脑膜炎模型来阐明Fpr2在不同感染部位的功能。与WT小鼠相比，Fpr2-/-小鼠表现出减少的炎症反应和细菌负荷，中性粒细胞募集增加。用AnxA1或LXA4预处理会损害白细胞募集，并增加WT中的细菌负荷和炎症反应，而不是经历STSLS的Fpr2-/-小鼠。这些结果表明，在STSLS期间，FPR2损害中性粒细胞募集，AnxA1或LXA4增强了这种损害。通过比较Fpr2在不同猪链球菌感染模型中的功能，炎症和NETs被发现阻碍猪链球菌脑膜炎的细菌清除，反过来加速STSLS中的细菌清除。因此,对中性粒细胞募集的干扰可能被用来开发针对这种感染性疾病的新疗法.
