Splenic Ly6G(high) mature and Ly6G(int) immature neutrophils contribute to eradication of S. pneumoniae.
Splenic Ly6G(high) mature and Ly6G(int) immature neutrophils contribute to eradication of S. pneumoniae.
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DOI：
10.1084/jem.20161621
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发表时间：
2017-05-01
期刊：
影响因子：
--
通讯作者：
Kubes P
中科院分区：
文献类型：
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作者：
Deniset JF;Surewaard BG;Lee WY;Kubes P
脾脏是保护免受包囊细菌侵害的组成部分。Deniset等人使用活体成像证明，脾脏中的中性粒细胞和巨噬细胞群体协调肺炎链球菌的快速清除，确保有足够的时间产生后续保护性抗体。脾脏对包囊性细菌感染起着不可或缺的保护作用。我们对相关机制的理解仅限于边缘区（MZ）B细胞产生的胸腺非依赖性（TI）抗体，尽管无脾患者在最初24小时内死于感染，但其他脾脏隔室（如红髓（RP））的贡献基本上未被探索，这表明重要的抗体非依赖性机制。在这项研究中，使用时间推移活体成像的脾脏，我们确定了一个嗜性肺炎链球菌在这个器官介导的组织驻留MZ和RP巨噬细胞和两个不同的脾中性粒细胞群体（Ly6Ghi和Ly6Gintermediate）居住在脾RP的保护作用。脾成熟中性粒细胞通过从RP巨噬细胞表面拔出细菌来介导脾中的肺炎球菌清除，RP巨噬细胞以补体依赖性方式捕获大多数细菌。这种中性粒细胞吞噬能力进一步增强后TI抗体的生产。脾中的常驻未成熟中性粒细胞（Ly6G中间体）在肺炎球菌刺激后经历紧急增殖和从其脾龛动员，以增加效应成熟中性粒细胞池。我们证明脾中性粒细胞与两个巨噬细胞群和MZ B细胞一起调节系统性S。肺炎通过互补机制清除。
The spleen is integral for protection against encapsulated bacteria. Using intravital imaging, Deniset et al. demonstrate that resident neutrophil and macrophage populations in the spleen coordinate the rapid clearance of Streptococcus pneumoniae, ensuring sufficient time for subseqent protective antibody production. The spleen plays an integral protective role against encapsulated bacterial infections. Our understanding of the associated mechanisms is limited to thymus-independent (TI) antibody production by the marginal zone (MZ) B cells, leaving the contribution of other splenic compartments such as the red pulp (RP) largely unexplored despite asplenic patients succumbing to the infection in the first 24 h, suggesting important antibody-independent mechanisms. In this study, using time-lapse intravital imaging of the spleen, we identify a tropism for Streptococcus pneumoniae in this organ mediated by tissue-resident MZ and RP macrophages and a protective role for two distinct splenic neutrophil populations (Ly6Ghi and Ly6Gintermediate) residing in the splenic RP. Splenic mature neutrophils mediated pneumococcal clearance in the spleen by plucking bacteria off the surface of RP macrophages that caught the majority of bacteria in a complement-dependent manner. This neutrophil phagocytic capacity was further enhanced after TI antibody production. Resident immature neutrophils (Ly6Gintermediate) in the spleen undergo emergency proliferation and mobilization from their splenic niche after pneumococcal stimulation to increase the effector mature neutrophil pool. We demonstrate that splenic neutrophils together with two macrophage populations and MZ B cells regulate systemic S. pneumoniae clearance through complementary mechanisms.