CSIR-Institute of Microbial Technology, Chandigarh, India.
Indian Institute of Technology, Ropar, India.
Front Immunol. 2020 May 19;11:726. doi: 10.3389/fimmu.2020.00726. eCollection 2020.
The generation of enduring protective immunity by vaccines is of utmost importance. Intriguingly, there is considerable variation in the efficacy of vaccines amongst individuals. Various studies have shown that normal flora of gastrointestinal tract plays a vital role in maintaining host homeostasis and immunity. Since gut microbiome is also extremely variable between individuals, we speculate that it might impact individual's response to vaccines. Consequently, we administered broad spectrum antibiotics cocktail to induce gut dysbiosis and monitored its impact on the generation of long-lasting memory T cells and thereby BCG vaccine efficacy. Interestingly, gut dysbiosis significantly decreased the activation of CD4 T cells and CD8 T cells. Further, there was decline in the frequency of memory CD4 T cells and CD8 T cells in lungs and secondary lymphoid organs of the vaccinated animals. Moreover, it dampened the IFN-γ and TNF-α secretion and proliferation of -specific T cells. Most importantly, dysbiosis hampered clearance in vaccinated animals, as evidenced by increase in the colony forming units (CFUs) in lungs and spleen. Our findings indicate that gut dysbiosis can be one of the major factors responsible for variable efficacy of TB vaccines across the world.
疫苗产生持久的保护免疫至关重要。有趣的是,疫苗在个体中的功效存在相当大的差异。各种研究表明,胃肠道的正常菌群在维持宿主内稳态和免疫方面起着至关重要的作用。由于肠道微生物组在个体之间也存在极大的差异,我们推测它可能会影响个体对疫苗的反应。因此,我们给予广谱抗生素鸡尾酒诱导肠道菌群失调,并监测其对长效记忆 T 细胞产生和卡介苗疫苗功效的影响。有趣的是,肠道菌群失调显著降低了 CD4 T 细胞和 CD8 T 细胞的激活。此外,在接种疫苗的动物的肺部和次级淋巴器官中,记忆性 CD4 T 细胞和 CD8 T 细胞的频率下降。此外,它抑制了 -特异性 T 细胞的 IFN-γ和 TNF-α分泌和增殖。最重要的是,菌群失调阻碍了接种疫苗动物的清除,这表现在肺部和脾脏中的菌落形成单位(CFUs)增加。我们的研究结果表明,肠道菌群失调可能是导致全球范围内结核疫苗功效差异的主要因素之一。