Eisenhut Michael
Luton & Dunstable University Hospital NHS Foundation Trust, Lewsey Road, Luton LU4ODZ, United Kingdom.
Med Hypotheses. 2015 Mar;84(3):189-93. doi: 10.1016/j.mehy.2014.12.019. Epub 2015 Jan 10.
The currently used vaccine for prevention of tuberculosis is Bacillus Calmette Guerin, which has been associated with a protective effect of 51% against tuberculosis. New vaccination strategies based on an enhancement of adaptive T-cell based immunity have been unsuccessful in increasing the efficiency of BCG immunisation. The proposed hypothesis is that a reduction of Mycobacterium (M.) tuberculosis infection in Bacillus Calmette Guerin immunized people is due to training of innate immunity. Evidence to support the hypothesis is a systematic review, which showed that BCG protects against M. tuberculosis infection as evident from negative interferon gamma release assay results in BCG immunised exposed people. BCG has been shown to enhance innate immunity in monocytes via nucleotide binding oligomerisation domain 2 receptor activation by muramyldipeptide. An alternative hypothesis may be that T-suppressor cells induced by BCG immunisation may be the reason for the absence of an interferon gamma response mimicking absence of infection in immunized people. In order to test the primary hypothesis an ultra-low dose mouse model of M. tuberculosis infection could be used. Innate immunity could be enhanced by administration of murabutide and groups with and without murabutide enhanced BCG immunisation and with and without elimination of T-suppressor cells compared. The contribution of training of innate immunity in reduction of infection could hereby be demonstrated by treatment of mice prior to immunisation with an inhibitor of epigenetic programming. Confirmation of the hypothesis could provide the foundation of a new approach to an improved vaccine against M. tuberculosis infection.
目前用于预防结核病的疫苗是卡介苗，它对结核病的保护效果为51%。基于增强适应性T细胞免疫的新疫苗接种策略在提高卡介苗免疫效率方面并未取得成功。提出的假设是，卡介苗免疫人群中结核分枝杆菌感染的减少是由于先天免疫的训练。支持该假设的证据是一项系统评价，该评价表明，卡介苗可预防结核分枝杆菌感染，这从卡介苗免疫的暴露人群中阴性干扰素γ释放试验结果可以明显看出。卡介苗已被证明可通过胞壁酰二肽激活核苷酸结合寡聚化结构域2受体来增强单核细胞的先天免疫。另一种假设可能是，卡介苗免疫诱导的T抑制细胞可能是免疫人群中缺乏干扰素γ反应（类似于未感染）的原因。为了检验主要假设，可以使用结核分枝杆菌感染的超低剂量小鼠模型。通过给予murabutide可以增强先天免疫，并比较有和没有murabutide增强卡介苗免疫以及有和没有消除T抑制细胞的组。在此之前，用表观遗传编程抑制剂对小鼠进行治疗，可以证明先天免疫训练在减少感染中的作用。对该假设的证实可为开发一种改进的抗结核分枝杆菌感染疫苗的新方法提供基础。
