巨噬细胞在树突状细胞启动抗布鲁氏菌免疫应答中的作用  

Macrophage-dependent initiation of immune response triggered by dendritic cells against Brucella

作　　者：董炳梅[1] 何媛娜[1] 王蓓[2] 韩丽滨[1] 耿彦生[2] 付景丽[1] 曹志然[2] 王家鑫[1] 

机构地区：[1]河北农业大学动物科技学院,保定071000 [2]河北大学医学部

出　　处：《中国人兽共患病学报》2009年第6期567-572,共6页Chinese Journal of Zoonoses

基　　金：国家“十一五”科技支撑计划项目(No.2006BAD04A10);河北省“千万吨奶工程”支撑技术研究(No.L07227146Z);河北省科学技术研究与发展计划(No.05240421D)

摘　　要：目的研究巨噬细胞(MΦ)在树突状细胞(DCs)启动抗布鲁氏菌免疫应答中的作用。方法用免疫组织化学染色法观察引流淋巴结内DCs的分布变化,用ELISA法检测阴道黏膜MΦ清除组和未清除组小鼠阴道接种布鲁氏菌疫苗后血清中IFN-γ、IL-4的含量,将MΦ与DCs体外负载布鲁氏菌疫苗,比较二者形态学变化。结果清除组接种疫苗12h～72h后,只见到少量的DCs散布于小鼠髂内淋巴结的皮质区和副皮质区;而未清除组阴道接种疫苗12h后,髂内淋巴结皮质区内DCs数量急剧增加,细胞密度增大并逐渐由皮质区向副皮质区迁移。清除组小鼠血清IFN-γ含量比未清除组有所下降,但显著高于PBS对照组(P<0.05);而各组小鼠血清IL-4含量保持基本一致。MΦ体外负载布鲁氏菌12h后胞质脱落,细胞核固缩,并释放出膜包小泡,而DCs却始终保持形态结构的完整。结论DCs启动抗布鲁氏菌Th1型免疫应答是一个MΦ依赖过程,MΦ吞噬布鲁氏菌后出现坏死性凋亡变化可能是这种依赖过程的机制。In order to demonstrate the function of macrophages （MФ） in the initiation of immune response triggered by dendritic cells （DCs） against Brucella, MФ in vaginal mucusa was depleted with clodronate-liposomes, and the dynamics of DCs in the iliac lymph nodes （ILNs） was immunohistologically investigated. Serum levels of IFN-γ and IL-4 were determined by ELISA. In vitro phagocytosis of Brucella either by MФ or DCs was performed. It was found that only fewer DCs in the cortex and paracortex of the ILNs were detected after intravaginal instillation of Brucella vaccine from 12h to 72h in the clodronate-liposomes treated mice. By contrast, the numbers of DCs in the ILNs rapidly increased and the DCs continued to migrate from cortex to paracortex zone in the PBS-liposomes treated mice. The levels of IFN-γ in serum were notably higher than that of normal mice that were instilled PBS in vagina, but significantly lower than the PBS-liposomes treated mice（P〈0.05）. The levels of IL-4 almost kept at the same levels in all group animals. The plasma membrane of MФ was ruptured and released some cellular debris and membrane-bound vacuoles after pulsed with Brucella in vitro. Furthermore, the nuclei of MФ were characteristic of shrinkage. In contrast, the structure of DCs remained intact after pulsed with Brucella vaccine in vitro. Collectively, these results suggest that Thl response triggered by DCs against Brucella is an MФ-dependent process. The possible underlying mechanism is that necroptotic MФ release some Brucella-eontaining vacuoles which are captured by DCs to initiate immune response.

关 键 词：巨噬细胞 布鲁氏菌 树突状细胞 迁移 坏死性凋亡 

分 类 号：R378.5[医药卫生—病原生物学]