Targeting the CD146/Galectin-9 axis protects the integrity of the blood-brain barrier in experimental cerebral malaria

作     者：Hongxia Duan Shuai Zhao Jianquan Xiang Chenhui Ju Xuehui Chen Irene Gramaglia Xiyun Yan Hongxia Duan;Shuai Zhao;Jianquan Xiang;Chenhui Ju;Xuehui Chen;Irene Gramaglia;Xiyun Yan

作者机构：Key Laboratory of Protein and Peptide PharmaceuticalInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Laboratory of Biochemistry and Molecular BiologySchool of Basic Medical SciencesSouthwest Medical UniversityLuzhou 646000 SichuanChina La Jolla Infectious Disease InstituteSan DiegoCAUSA Joint Laboratory of Nanozymes in Zhengzhou UniversitySchool of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001 HenanChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2021年第18卷第10期

页      面：2443-2454页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：This work was supported in part by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant no.XDB29040101) grants from the National Natural Science Foundation of China(Grant nos.31530026 and 31770793) grants from the Beijing Natural Science Foundation of China(Grant no.7192123) the National Science and Technology Major Project(Grant no.2018ZX10101004002004) the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2018122) 

主　　题：CD146 BBB experimental cerebral malaria 

摘      要：Cerebral malaria(CM)is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum,in which the destruction of the blood–brain barrier(BBB)is the main cause of ***,increasing evidence has shown that antimalarial drugs,the current treatment for CM,do little to protect against CM-induced BBB ***,a means to alleviate BBB dysfunction would be a promising adjuvant therapy for *** adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates ***,we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria(eCM).Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells(RBCs)and/or proinflammatory lymphocytes in CNS blood vessels,thereby promoting the disruption of BBB *** studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and *** of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM,such as limb paralysis,brain vascular leakage,and *** addition,AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with *** together,our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.