Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis.
Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis.
复制标题
在猪链球菌诱发的脑膜炎小鼠模型中，Annexin A1 通过 Fpr2 减弱中性粒细胞迁移和 IL-6 表达。
DOI：
10.1128/iai.00680-20
复制
发表时间：
2021-02-16
影响因子：
3.1
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Ni C;Gao S;Zheng Y;Liu P;Zhai Y;Huang W;Jiang H;Lv Q;Kong D;Jiang Y
猪链球菌血清型 2 是细菌性脑膜炎的重要致病原因，细菌性脑膜炎是一种具有神经系统后遗症和高死亡率的危及生命的疾病。必须精确调节猪链球菌感染引发的炎症，以防止进一步的组织损伤。猪链球菌血清型 2 是细菌性脑膜炎的重要致病原因，细菌性脑膜炎是一种具有神经系统后遗症和高死亡率的危及生命的疾病。必须精确调节猪链球菌感染引发的炎症，以防止进一步的组织损伤。作为糖皮质激素抗炎介质，膜联蛋白 A1 (AnxA1) 主要通过甲酰肽受体 2 (Fpr2) 发挥作用，减轻外周系统的炎症。在这项研究中，我们评估了 AnxA1 和 Fpr2 在猪链球菌脑膜炎小鼠模型中的作用，该模型是通过 Fpr2 缺陷型 (Fpr2−/−) 和野生型 (WT) 小鼠脑池内感染创建的。我们发现，与 WT 小鼠相比，Fpr2−/− 小鼠对猪链球菌脑膜炎高度敏感，表现出炎症细胞因子水平、细菌传播和中性粒细胞迁移增加。此外，AnxA1 通过 Fpr2 发挥抗炎作用，例如减弱白细胞浸润、炎症介质的产生以及大脑中星形胶质细胞或小胶质细胞的激活。重要的是，我们发现 AnxA1 的抗迁移功能通过 Fpr2 降低中性粒细胞与内皮的粘附。最后，一项体外研究表明，AnxA1 可能通过 Fpr2/p38/COX-2 途径抑制白细胞介素 6 (IL-6) 的表达。这些数据表明，Fpr2 是一种抗炎受体，可调节患有猪链球菌脑膜炎的小鼠的中性粒细胞迁移，并确定 AnxA1 是一种潜在的治疗选择。
Streptococcus suis serotype 2 is a crucial pathogenic cause of bacterial meningitis, a life-threatening disease with neurological sequelae and high rates of mortality. Inflammation triggered by S. suis infection must be precisely regulated to prevent further tissue damage. Streptococcus suis serotype 2 is a crucial pathogenic cause of bacterial meningitis, a life-threatening disease with neurological sequelae and high rates of mortality. Inflammation triggered by S. suis infection must be precisely regulated to prevent further tissue damage. As a glucocorticoid anti-inflammatory mediator, annexin A1 (AnxA1) mainly acts through formyl peptide receptor 2 (Fpr2) to alleviate inflammation in the peripheral system. In this study, we evaluated the roles of AnxA1 and Fpr2 in a mouse model of S. suis meningitis created via intracisternal infection in Fpr2-deficient (Fpr2−/−) and wild-type (WT) mice. We revealed that Fpr2−/− mice were highly susceptible to S. suis meningitis, displaying increased inflammatory cytokine levels, bacterial dissemination, and neutrophil migration compared with WT mice. Additionally, AnxA1 exerted anti-inflammatory effects through Fpr2, such as attenuation of leukocyte infiltration, inflammatory mediator production, and astrocyte or microglial activation in the brain. Importantly, we found that the antimigratory function of AnxA1 decreases neutrophil adherence to the endothelium through Fpr2. Finally, an in vitro study revealed that AnxA1 potentially suppresses interleukin-6 (IL-6) expression through the Fpr2/p38/COX-2 pathway. These data demonstrated that Fpr2 is an anti-inflammatory receptor that regulates neutrophil migration in mice with S. suis meningitis and identified AnxA1 as a potential therapeutic option.