Fpr2/CXCL1/2 Controls Rapid Neutrophil Infiltration to Inhibit Streptococcus agalactiae Infection.
Fpr2/CXCL1/2 Controls Rapid Neutrophil Infiltration to Inhibit Streptococcus agalactiae Infection.
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DOI：
10.3389/fimmu.2021.786602
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发表时间：
2021
影响因子：
7.3
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Sun Z;Huang W;Zheng Y;Liu P;Yang W;Guo Z;Kong D;Lv Q;Zhou X;Du Z;Jiang H;Jiang Y
无乳链球菌，也称为B组链球菌（GBS），可引起肺炎、脑膜炎和菌血症，使其成为可增加新生儿和免疫缺陷个体死亡风险的病原体。中性粒细胞是宿主对这些感染的先天免疫防御的第一道屏障。Fpr 2（甲酰肽受体2）是中性粒细胞的重要趋化性受体，尽管其活化会引起促炎和抗炎作用。在这项研究中，我们发现没有Fpr 2受体的小鼠对GBS感染高度易感。这些小鼠表现出对中性粒细胞的趋化性降低、中性粒细胞的杀菌能力降低和高死亡率。RNA-seq和Luminex检测结果表明，Fpr 2激活下游关键信号分子，产生趋化因子CXCL 1/2，趋化中性粒细胞，与Fpr 2-/-一样，CXCL 1/2或中性粒细胞的耗竭削弱了宿主抵抗GBS感染的能力。总之，这些数据表明，Fpr 2有助于宿主控制GBS感染的能力，并且Fpr 2的缺乏与趋化因子CXCL 1和CXCL 2的产生以及中性粒细胞募集期间的选择性损伤相关。本文阐明Fpr 2作为一种趋化性受体，不仅可以直接趋化中性粒细胞，还可以调节趋化因子的产生，从而控制趋化性中性粒细胞的感染。
Streptococcus agalactiae, also known as group B streptococcus (GBS), can cause pneumonia, meningitis, and bacteremia, making it a pathogen that can increase the risk of death in newborns and immunodeficient individuals. Neutrophils are the first barrier to a host’s innate immune defense against these infections. Fpr2(Formyl peptide receptor 2) is an important chemotactic receptor of neutrophils, though its activation would cause pro- and anti-inflammatory effects. In this study, we found that mice without Fpr2 receptor were highly susceptible to GBS infections. These mice demonstrated decreased chemotaxis to neutrophils, decreased bactericidal ability of neutrophils, and high mortality. RNA-seq and Luminex assay indicated that Fpr2 activates key signal molecules downstream and produces chemokines CXCL1/2 to chemotaxis neutrophils. Like Fpr2-/-, CXCL1/2 or neutrophil depletion impairs host’s ability to defend against GBS infection. Altogether, these data indicate that Fpr2 contributes to a host’s ability to control GBS infection and that a lack of Fpr2 was associated with selective impairment during the production of chemokines CXCL1 and CXCL2 as well as neutrophil recruitment. Here, We clarified that Fpr2, as a chemotactic receptor, could not only directly chemotactic neutrophils, but also regulate the production of chemokines to control infection by chemotactic neutrophils.
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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。
影响因子：
3.1
作者：
Ni C;Gao S;Zheng Y;Liu P;Zhai Y;Huang W;Jiang H;Lv Q;Kong D;Jiang Y
通讯作者：
Jiang Y
影响因子：
13
作者：
De Buck M;Gouwy M;Wang JM;Van Snick J;Proost P;Struyf S;Van Damme J
通讯作者：
Van Damme J
影响因子：
5.5
作者：
Pellme, Sara;Morgelin, Matthias;Karlsson, Anna
通讯作者：
Karlsson, Anna
影响因子：
64.8
作者：
Carvelli, Julien;Demaria, Olivier;Vivier, Eric
通讯作者：
Vivier, Eric
影响因子：
3.1
作者：
Biondo, C.;Mancuso, G.;Beninati, C.
通讯作者：
Beninati, C.