State Key Laboratory of Bio-Control, Higher Education Mega Center, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Front Immunol. 2019 Aug 22;10:1991. doi: 10.3389/fimmu.2019.01991. eCollection 2019.
Temperature is one of the major factors that affect the outbreak of infectious disease. Lines of evidences have shown that virulence factors can be controlled by thermo-sensors in bacterial pathogens. However, how temperature influences host's responses to the pathogen is still largely unexplored, and the study of this might pave the way to develop strategies to manage pathogenic bacterial infection. In the present study, we show that finfish , the crucian carp that is tolerant to a wide range of temperatures, is less susceptible to bacterial infection when grown in 20°C than in 30°C. The different responses of to bacterial infection could be partially explained by the distinct metabolisms under the specific temperatures: shows elevated tricarboxylic acid cycle (TCA cycle) but decreased taurine and hypotaurine metabolism as well as lower biosynthesis of unsaturated fatty acids at 30°C. The decreased abundance of palmitate, threonine, and taurine represents the most characteristic metabolic feature. Consistently, exogenous palmitate, threonine, or taurine enhances the survival of to bacterial infection at 30°C in a dose-dependent manner. This effect could be attributed to the inhibition on the TCA cycle by the three metabolites. This notion is further supported by the fact that low concentration of malonate, a succinate dehydrogenase inhibitor, increases the survival of at 30°C as well. On the other hand, addition of the three metabolites rescued the decreased expression of pro-inflammatory cytokines including TNF-α1, TNF-α2, IL-1β1, IL-1β2, and lysozyme at 30°C. Taken together, our results revealed an unexpected relationship between temperature and metabolism that orchestrates the immune regulation against infection by bacterial pathogens. Thus, this study shed light on the modulation of finfish physiology to fight against bacterial infection through metabolism.
温度是影响传染病爆发的主要因素之一。有证据表明,细菌病原体中的毒力因子可以被热传感器控制。然而,温度如何影响宿主对病原体的反应在很大程度上仍未得到探索,而对这方面的研究可能为开发管理致病性细菌感染的策略铺平道路。在本研究中,我们表明,鲫鱼是一种能耐受广泛温度范围的鱼类,当在 20°C 下生长时,比在 30°C 下生长时对细菌感染的敏感性更低。在特定温度下,鲫鱼对细菌感染的不同反应可以部分解释为不同的代谢反应:在 30°C 下,鲫鱼表现出升高的三羧酸循环(TCA 循环),但降低了牛磺酸和次牛磺酸代谢以及不饱和脂肪酸的生物合成。棕榈酸、苏氨酸和牛磺酸的丰度降低代表了最具特征性的代谢特征。一致地,外源性棕榈酸、苏氨酸或牛磺酸以剂量依赖的方式增强了鲫鱼在 30°C 下对细菌感染的存活能力。这种效应可以归因于三种代谢物对 TCA 循环的抑制。这一观点进一步得到了以下事实的支持:低浓度的丙二酸,一种琥珀酸脱氢酶抑制剂,也能增加鲫鱼在 30°C 下的存活率。另一方面,三种代谢物的添加挽救了在 30°C 时下调的促炎细胞因子的表达,包括 TNF-α1、TNF-α2、IL-1β1、IL-1β2 和溶菌酶。总之,我们的结果揭示了温度和代谢之间的一种意想不到的关系,这种关系协调了宿主对细菌病原体感染的免疫调节。因此,本研究揭示了通过代谢来调节鱼类生理学以对抗细菌感染的机制。