Elias Daniel, Akuffo Hannah, Pawlowski Andrzej, Haile Melles, Schön Thomas, Britton Sven
Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, 17177 Stockholm, Sweden.
Vaccine. 2005 Feb 3;23(11):1326-34. doi: 10.1016/j.vaccine.2004.09.038.
We hypothesized that the ability of BCG vaccination to protect against Mycobacterium tuberculosis is less in hosts exposed to chronic helminthes infection compared to unexposed individuals. To test this hypothesis we evaluated the efficacy of BCG vaccination in protecting against M. tuberculosis challenge in Schistosoma mansoni pre-infected mice by analyzing their ability to limit the replication of TB bacilli in the lung and liver and the histology of lung sections. The results show that BCG vaccinated mice with prior S. mansoni infection show significantly higher number of colony forming units of TB bacilli as well as significant reduction in air exchange area in the lung compared to controls. In addition, spleen cells from S. mansoni infected mice were found to produce significantly less IFN-gamma and nitric oxide when stimulated in vitro with PPD and several fold higher soluble egg antigen (SEA) and Concanavalin A induced IL-4 and IL-5 secretion. Taken together, our data show that S. mansoni infection reduces the protective efficacy of BCG vaccination against M. tuberculosis possibly by attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile.
我们推测,与未接触过慢性蠕虫感染的宿主相比,接种卡介苗预防结核分枝杆菌的能力在接触过慢性蠕虫感染的宿主中较弱。为了验证这一假设,我们通过分析曼氏血吸虫预感染小鼠限制结核杆菌在肺和肝脏中复制的能力以及肺组织切片的组织学情况,评估了卡介苗接种对曼氏血吸虫预感染小鼠抵御结核分枝杆菌攻击的效果。结果显示,与对照组相比,先前感染过曼氏血吸虫的卡介苗接种小鼠的结核杆菌菌落形成单位数量显著更高,且肺部气体交换面积显著减小。此外,发现曼氏血吸虫感染小鼠的脾细胞在体外用结核菌素纯蛋白衍生物(PPD)刺激时产生的γ干扰素和一氧化氮显著减少,而可溶性虫卵抗原(SEA)和刀豆球蛋白A诱导的白细胞介素-4和白细胞介素-5分泌则高出数倍。综上所述,我们的数据表明,曼氏血吸虫感染可能通过减弱对分枝杆菌抗原的保护性免疫反应和/或使总体免疫反应偏向辅助性T细胞2(Th2)型,从而降低卡介苗接种对结核分枝杆菌的保护效果。