髓系细胞缺失ATG5对疟原虫特异性CD4+T细胞免疫记忆形成的影响  

Effects of ATG5 deficiency in myeloid cell on immune memory formation of Plasmodium specific CD4+T cells

作　　者：李秀秀 高源利 范永玲 刘太平 郭帅 方佳芩 徐文岳 LI Xiuxiu;GAO Yuanli;FAN Yongling;LIU Taiping;GUO Shuai;FANG Jiaqin;XU Wenyue(Department of Pathogenic Biology,Army Medical University,Chongqing 400038,China)

机构地区：[1]陆军军医大学基础医学院病原生物学教研室,重庆400038

出　　处：《免疫学杂志》2023年第9期777-782,796,共7页Immunological Journal

基　　金：国家自然科学基金(82072299)。

摘　　要：目的研究髓系细胞缺失ATG5对疟原虫特异性CD4^(+)T细胞免疫记忆形成的影响。方法构建髓系细胞特异缺失ATG5的条件敲除小鼠,在其感染约氏疟原虫Plasmodium yoelii(P.yoelii)17XNL自愈后1个月、3个月和6个月分别再次感染该虫株,观察其原虫率变化。同时采用流式细胞术检测髓系细胞ATG5条件缺失感染自愈小鼠疟原虫特异性免疫记忆CD4^(+)T细胞频率和数量的变化。结果成功构建髓系细胞ATG5条件缺失实验小鼠(ATG5^(f/f)-LysM cre^(+))。与对照组(ATG5^(f/f)-LysM cre^(-))相比,初次感染P.y 17XNL的实验组小鼠(ATG5^(f/f)-LysM cre^(+))原虫血症明显低于对照组小鼠(ATG5^(f/f)-LysM cre^(-))。在上述感染小鼠自愈后1个月、3个月和6个月再次感染P.y 17XNL,结果发现感染小鼠原虫血症与初次感染相比,均显著降低,且所有感染小鼠在攻击后6~8 d内完全清除体内疟原虫。流式检测后发现,ATG5^(f/f)-LysM cre^(+)与ATGf/f-LysM cre^(-)小鼠感染自愈后3个月或6个月,其脾脏疟原虫特异性免疫记忆CD4^(+)T细胞频率和数量均无统计学差异。结论P.y 17XNL感染自愈小鼠可以有效诱导宿主免疫记忆,但髓系细胞缺失ATG5不影响疟原虫特异性CD4^(+)T细胞免疫记忆形成。This study was performed to investigate the effect of ATG5 deficiency in myeloid cells on the immune memory formation of Plasmodium specific CD4^(+)T cells.The conditional knockout mice with myeloid cell specific deletion of ATG5 were constructed and re-infected with Plasmodium yoelii(P.yoelii)17XNL at 1 month,3 months and 6 months after self-healing,and the parasite prevalence was observed.At the same time,the frequency and number of CD4^(+)T cells of specific immune memory in self-healing mice with myeloid cells ATG5 conditional deletion were detected by flow cytometry.Data showed that myeloid ATG5 conditional deletion mice(ATG5^(f/f)-LysM cre^(+))was successfully generated.Compared with the control group(ATG5^(f/f)-LysM cre^(-)),the parasitemia in the experimental group with primary infection of P.y 17XNL was significantly lower than that in the control group.Furthermore,the mice were re-infected with P.y 17XNL one month,three months and six months after selfrecovery,and the parasitemia of the re-infected mice was significantly lower than that of the primary infected mice,and all the infected mice completely cleared Plasmodium in 6-8 days.Flow cytometry analysis showed that there was no significant difference in the frequency and number of CD4^(+)T cells in the spleen of ATG5^(f/f)-LysM cre^(+)and ATG5^(f/f)-LysM cre^(-)mice at 3 or 6 months after self-healing.Taken together,P.y 17XNL infection can effectively induce host immune memory in self-healing mice,while deficiency of ATG5 in myeloid cells does not affect the immune memory formation of Plasmodium specific CD4^(+)T cells.

关 键 词：约氏疟原虫17XNL 髓系细胞 ATG5 疟原虫特异性CD4+T细胞 免疫记忆 

分 类 号：R392.1[医药卫生—免疫学]