College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China.
Int J Mol Sci. 2024 Aug 14;25(16):8866. doi: 10.3390/ijms25168866.
Besides their direct bactericidal effect, antibiotics have also been suggested to stimulate the host immune response to defend against pathogens. However, it remains unclear whether any antibiotics may stimulate the host immune response by affecting bacterial activity. In this study, reasoning that genetic mutations inhibit bacterial activities and, thereby, may mimic the effects of antibiotics, we performed genome-wide screening and identified 77 genes whose inactivation induces , representing an innate immune and detoxification response. Further analyses reveal that this host immune response can clearly be induced through either inactivating the respiratory chain via the bacterial mutation or using the antibiotic Q203, which is able to enhance host survival when encountering the pathogen . Mechanistically, the innate immune response triggered by both the mutation and Q203 is found to depend on the host brain response, as evidenced by their reliance on the host neural gene , which is required for neurotransmitter release in head neurons. Therefore, our findings elucidate the critical involvement of the microbiota-brain axis in modulating the host immune response, providing mechanistic insights into the role of antibiotics in triggering the host immune response and, thus, facilitating host defense against pathogens.
除了直接杀菌作用外，抗生素还被认为可以通过刺激宿主免疫反应来抵御病原体。然而，目前尚不清楚是否有任何抗生素可以通过影响细菌活性来刺激宿主免疫反应。在这项研究中，我们推断基因突变抑制细菌活性，从而可能模拟抗生素的作用，进行了全基因组筛选，确定了 77 个基因的失活会诱导 ，这代表了一种先天免疫和解毒反应。进一步的分析表明，这种宿主免疫反应可以通过细菌基因突变或使用抗生素 Q203 来明显诱导，当遇到病原体时，Q203 能够增强宿主的存活率。从机制上讲，无论是突变还是 Q203 触发的先天免疫反应都依赖于宿主的大脑反应，这可以从它们依赖于宿主神经基因中得到证明，该基因是头部神经元中神经递质释放所必需的。因此，我们的研究结果阐明了微生物群-大脑轴在调节宿主免疫反应中的关键作用，为抗生素在触发宿主免疫反应中的作用提供了机制上的见解，并有助于宿主防御病原体。
