Streptococcus pneumoniae endopeptidase O induces trained immunity and confers protection against various pathogenic infections

作者全名：Xu, Wenlong; Yuan, Yuan; Shu, Zhaoche; Guo, Ting; Liu, Bichen; Xiao, Jiangming; Li, Lian; Yin, Yibin; Zhang, Xuemei

作者地址：[Xu, Wenlong; Yuan, Yuan; Shu, Zhaoche; Guo, Ting; Liu, Bichen; Xiao, Jiangming; Li, Lian; Yin, Yibin; Zhang, Xuemei] Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med, Minist Educ, Chongqing 400016, Peoples R China

通信作者：Zhang, XM (通讯作者)，Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med, Minist Educ, Chongqing 400016, Peoples R China.

来源：CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001237894600001

JCR分区：Q2

影响因子：4.5

年份：2024

卷号：263

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Trained immunity; Macrophage; B lymphocyte; G-CSF; Streptococcus pneumoniae endopeptidase O; (PepO)

摘要：Antibiotic resistance and the surge of infectious diseases during the pandemic present significant threats to human health. Trained immunity emerges as a promising and innovative approach to address these infections. Synthetic or natural fungal, parasitic and viral components have been reported to induce trained immunity. However, it is not clear whether bacterial virulence proteins can induce protective trained immunity. Our research demonstrates Streptococcus pneumoniae virulence protein PepO, is a highly potent trained immunity inducer for combating broad-spectrum infection. Our findings showcase that rPepO training confers robust protection to mice against various pathogenic infections by enhancing macrophage functionality. rPepO effectively re-programs macrophages, re-configures their epigenetic modifications and bolsters their immunological responses, which is independent of T or B lymphocytes. In vivo and in vitro experiments confirm that trained macrophage-secreted complement C3 activates peritoneal B lymphocyte and enhances its bactericidal capacity. In addition, we provide the first evidence that granulocyte colony-stimulating factor (G-CSF) derived from trained macrophages plays a pivotal role in shaping central-trained immunity. In summation, our research demonstrates the capability of rPepO to induce both peripheral and central trained immunity in mice, underscoring its potential application in broad-spectrum anti-infection therapy. Our research provides a new molecule and some new target options for infectious disease prevention.

基金机构：Program for Youth Innovation Future Medicine, Chongqing Medical University [W0148]; National Natural Science Foundation of China [81571622]

基金资助正文：This study was supported by the Program for Youth Innovation Future Medicine, Chongqing Medical University (No. W0148 to Z.X.M.) , the National Natural Science Foundation of China (No. 81571622 to Z.X. M.) .