BALB/c mice display more enhanced BCG vaccine induced Th1 and Th17 response than C57BL/6 mice but have equivalent protection

BALB/c mice display more enhanced BCG vaccine induced Th1 and Th17 response than C57BL/6 mice but have equivalent protection
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DOI:
10.1016/j.tube.2014.10.012
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发表时间:
2015-01-01
期刊:
影响因子:
3.2
通讯作者:
Hogarth, Philip J.
Hogarth, Philip J.
中科院分区:
医学4区
文献类型:
--
作者:
Garcia-Pelayo, M. Carmen;Bachy, Veronique S.;Hogarth, Philip J.

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人们普遍认为,近交系小鼠BALB/c(H - 2d)和C57BL/6(H - 2b)对分枝杆菌感染的反应中,T辅助细胞反应呈现明显的极化,C57BL/6倾向于Th1反应,而BALB/c倾向于Th2反应。我们在一个卡介苗免疫、牛分枝杆菌攻击模型中对此进行了研究。免疫后,测定了肺和脾细胞在体外用七种分泌型、免疫原性重组分枝杆菌蛋白混合物再次刺激后的细胞因子反应。在肺和脾中,BALB/c细胞产生的干扰素 - γ至少比C57BL/6细胞多2倍,白细胞介素 - 2和白细胞介素 - 17最多比C57BL/6细胞多7倍,而白细胞介素 - 10的产生在C57BL/6小鼠中则相应增加。这些数据表明,与文献报道相反,特定的分枝杆菌抗原在卡介苗接种后能够在BALB/c小鼠中诱导强烈的Th1和Th17反应,而在C57BL/6小鼠中,Th1反应部分被白细胞介素 - 10所抵消。在随后的低剂量牛分枝杆菌攻击后,通过对肺部和向脾脏扩散情况的检测,BALB/c和C57BL/6小鼠的保护作用相当,这表明卡介苗诱导的免疫在两种品系中是等效的。因此,不同的免疫反应似乎在保护作用中没有起到作用,而且进一步来说,还有尚未确定的特异性免疫反应起着重要作用。英国皇家版权所有(C)2014,由爱思唯尔有限公司出版。这是一篇在知识共享署名 - 非商业性使用 - 禁止演绎许可协议下的开放获取文章
It is generally assumed that the inbred mouse strains BALB/c (H-2(d)) and C57BL/6 ( H-2(b)) respond to mycobacterial infection with distinct polarisation of T helper responses, with C57BL/6 predisposed to Th1 and BALB/c to Th2. We investigated this in a BCG-immunisation, Mycobacterium bovis challenge model. Following immunisation, lung and spleen cell cytokine responses to in vitro re-stimulation with a cocktail of seven secreted, immunogenic, recombinant mycobacterial proteins were determined. In both lung and spleen, BALB/c cells produced at least 2-fold more IFN-gamma, and up to 7-fold more IL-2 and IL-17 than C57BL/6 cells, whereas IL-10 production was reciprocally increased in C57BL/6 mice. These data suggest that, contrary to reports in the literature, specific mycobacterial antigens are able to induce strong Th1 and Th17 responses in BALB/c mice following BCG vaccination, whilst in C57BL/6 mice, the Th1 response is partly counterbalanced by IL-10. After subsequent M. bovis low dose challenge, protection, as measured in the lungs and dissemination to the spleen, was equivalent in BALB/c and C57BL/6 mice, indicating that BCG-induced immunity was equivalent in both strains. Thus, the differential immune responses do not appear to have a role in protection, but further, as yet unidentified, specific immune responses play a significant role. Crown Copyright (C) 2014 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license