Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
Mol Ecol. 2019 Dec;28(24):5360-5372. doi: 10.1111/mec.15293. Epub 2019 Nov 21.
Immune responses evolve to balance the benefits of microbial killing against the costs of autoimmunity and energetic resource use. Models that explore the evolution of optimal immune responses generally include a term for constitutive immunity, or the level of immunological investment prior to microbial exposure, and for inducible immunity, or investment in immune function after microbial challenge. However, studies rarely consider the functional form of inducible immune responses with respect to microbial density, despite the theoretical dependence of immune system evolution on microbe- versus immune-mediated damage to the host. In this study, we analyse antimicrobial peptide (AMP) gene expression from seven wild-caught flour beetle populations (Tribolium spp.) during acute infection with the virulent bacteria Bacillus thuringiensis (Bt) and Photorhabdus luminescens (P.lum) to demonstrate that inducible immune responses mediated by the humoral IMD pathway exhibit natural variation in both microbe density-dependent and independent temporal dynamics. Beetle populations that exhibited greater AMP expression sensitivity to Bt density were also more likely to die from infection, while populations that exhibited higher microbe density-independent AMP expression were more likely to survive P. luminescens infection. Reduction in pathway signalling efficiency through RNAi-mediated knockdown of the imd gene reduced the magnitude of both microbe-independent and dependent responses and reduced host resistance to Bt growth, but had no net effect on host survival. This study provides a framework for understanding natural variation in the flexibility of investment in inducible immune responses and should inform theory on the contribution of nonequilibrium host-microbe dynamics to immune system evolution.
免疫反应的进化旨在平衡杀死微生物的益处与自身免疫和能量资源利用的成本。探索最佳免疫反应进化的模型通常包括组成性免疫的术语，即微生物暴露前的免疫投资水平，以及诱导性免疫的术语，即在微生物挑战后对免疫功能的投资。然而，尽管免疫系统的进化取决于微生物对宿主的损害与免疫介导的损害，但研究很少考虑诱导性免疫反应对微生物密度的函数形式。在这项研究中，我们分析了来自七个野外采集的面粉甲虫种群（Tribolium 属）的抗菌肽（AMP）基因表达，这些甲虫种群在受到毒力细菌苏云金芽孢杆菌（Bt）和发光杆菌（P.lum）的急性感染期间，以证明由体液 IMD 途径介导的诱导性免疫反应在微生物密度依赖性和非依赖性的时间动态方面表现出自然变异。对 Bt 密度表现出更高 AMP 表达敏感性的甲虫种群也更有可能因感染而死亡，而表现出更高微生物密度独立 AMP 表达的种群则更有可能在感染发光杆菌时存活。通过 RNAi 介导的 imd 基因敲低降低途径信号效率，降低了微生物非依赖性和依赖性反应的幅度，并降低了宿主对 Bt 生长的抗性，但对宿主存活没有净影响。本研究为理解诱导性免疫反应投资灵活性的自然变异提供了一个框架，并应告知关于非平衡宿主-微生物动态对免疫系统进化的贡献的理论。
