Kleinnijenhuis Johanneke, Quintin Jessica, Preijers Frank, Benn Christine Stabell, Joosten Leo A B, Jacobs Cor, van Loenhout Joke, Xavier Ramnik J, Aaby Peter, van der Meer Jos W M, van Crevel Reinout, Netea Mihai G
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Innate Immun. 2014;6(2):152-8. doi: 10.1159/000355628. Epub 2013 Oct 30.
We have recently shown that BCG (Bacillus Calmette-Guérin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named 'trained immunity'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses.
我们最近发现，在健康志愿者中接种卡介苗（Bacillus Calmette-Guérin，BCG）可诱导单核细胞发生表观遗传重编程，从而在接种疫苗后长达3个月的时间里，增强对非相关病原体的细胞因子产生。这种现象被命名为“训练性免疫”。在本研究中，我们评估了接种卡介苗1年后，其是否能够对训练性免疫以及异源T辅助细胞1（Th1）和Th17免疫反应产生持久影响。接种疫苗后2周和3个月时，对分枝杆菌或非相关病原体产生的TNFα和IL-1β水平较高，但接种疫苗1年后这些影响不太明显。然而，接种疫苗1年后恢复的单核细胞中模式识别受体如CD14、Toll样受体4（TLR4）和甘露糖受体的表达增加，这与用TLR4配体脂多糖刺激后促炎细胞因子产生的增加相关。即使在接种卡介苗1年后，对非分枝杆菌刺激的Th1（IFN-γ）和Th17（IL-17和IL-22）免疫反应的异源产生仍显著升高。总之，卡介苗在先天性训练性免疫水平和异源Th1/Th17反应水平上均诱导免疫系统发生持续变化，这些变化与对感染的非特异性反应相关。
