PMN-MDSC:A Culprit Behind Immunosenescence and Increased Susceptibility to Clostridioides difficile Infection During Aging  

作　　者：Jianmin Wu Ming Zhang Hao Zhang Mingxuan Sheng Jiazeng Sun Fang Wu Haina Gao Lishui Chen Zhili Li Qiyu Tian Longjiao Zhu Bing Fang 

机构地区：[1]Beijing Advanced Innovation Center for Food Nutrition and Human Health,Beijing 100191,China [2]School of Food and Health,Beijing Technology and Business University,Beijing 100048,China [3]School of Life Sciences,Henan University,Zhengzhou 475004,China [4]Department of Basic Medical Sciences,Purdue University,West Lafayette,IN 47907,USA [5]Food Laboratory of Zhongyuan,Louhe 462300,China [6]Department of Molecular Pathobiology,New York University,New York,NY 10010,USA

出　　处：《Engineering》2024年第11期59-73,共15页工程（英文）

基　　金：supported by the National Key Research and Development Program of China(2022YFF1100504);the 111 project from the Education Ministry of China(B18053);the National Natural Science Foundation of China(32101938 and 32302758);the China Postdoctoral Science Foundation(2022M723422);the Postdoctoral Fellowship Program of CPSF(GZB20230848).

摘　　要：Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.

关 键 词：PMN-MDSC IMMUNOSENESCENCE AGING Mass cytometry Clostridioides difficile 

分 类 号：R392[医药卫生—免疫学]