幼稚中性粒细胞在疟原虫慢性感染中的作用研究  

The role of immature neutrophils in controlling chronic Plasmodium chabaudi infection

作　　者：方佳芩 刘太平 徐文岳 FANG Jiaqin;LIU Taiping;XU Wenyue(Department of Pathogenic Biology,Army Medical University(Third Military 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404100

出　　处：《免疫学杂志》2024年第10期745-751,共7页Immunological Journal

基　　金：重庆市自然科学基金(CSTB2023NSCQ-MSX0788)。

摘　　要：目的探讨幼稚中性粒细胞在夏氏疟原虫(Plasmodium chabaudi,P.c)慢性感染中的作用及其机制。方法单细胞测序结合流式细胞术检测自然感染过程中C57BL/6J小鼠脾脏幼稚中性粒细胞的动态变化及其S100A9表达。应用帕奎莫德去除幼稚中性粒细胞,流式细胞术检测其对抗疟原虫免疫应答的影响。采用单细胞测序结合流式细胞术检测单核/巨噬细胞变化。应用氯磷酸盐脂质体(clodronate liposomes,CLs)去除脾脏髓系细胞,监测小鼠原虫血症及存活率。结果幼稚中性粒细胞频率及数量在P.c慢性期显著增加(P<0.001);与对照组相比,在急性期给药使小鼠慢性期原虫血症显著增高(P<0.001)且小鼠脾脏幼稚中性粒细胞和单核细胞减少(P<0.05);CLs处理后小鼠单核细胞及巨噬细胞减少(P<0.05),原虫血症升高(P<0.01)。结论疟原虫感染慢性期新生大量幼稚中性粒细胞,该细胞可能通过影响单核细胞发挥抗疟原虫免疫保护作用。Objective The aim of this study was to investigate the effect of immature neutrophils on chronic Plasmodium chabaudi(P.c)infection.Methods Single-cell sequencing combined with flow cytometry was used to detect dynamic changes in immature neutrophils and its S100A9 protein expression during P.c infection.Mice were intragastrically administered Paquinimod to deplete the immature neutrophils.Flow cytometry was used to assess its effect on the immune response against Plasmodium chabaudi.Single-cell sequencing and flow cytometry were conducted on splenocytes to examine changes of monocytes/macrophages.Results Clodronate liposomes(CLs)were administered and parasitemia and survival rates were monitored.The data showed that the frequency and number of immature neutrophils increased significantly during the chronic phase of P.c infection.Parasitemia was significantly elevated in the drug-treatment group,accompanied by a reduction in the frequency and number of immature neutrophils and monocytes.After CLs treatment,monocytes and macrophages decreased and parasitemia increased.Conclusion Taken together,a large number of immature neutrophils are newly generated during the chronic phase of Plasmodium chabaudi infection,and they may exert an anti-Plasmodium chabaudi protective role through an impact on monocytes.

关 键 词：中性粒细胞 疟原虫 慢性感染 单核细胞 

分 类 号：R382.3[医药卫生—医学寄生虫学]