Tang Ting, Yang Lan, Ma Liya, Ren Yu, Li Mengnan, Guo Shufan, Wang Xin, Zhang Yuming, Liu Fengsong
The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, 071002, China.
Hebei Basic Science Center for Biotic Interaction, Hebei University, Baoding, 071002, China.
BMC Biol. 2025 Jul 22;23(1):220. doi: 10.1186/s12915-025-02324-6.
The activation of the immune system by pathogens imposes significant energetic costs on hosts, which may result in the diversion of resources away from other non-essential biological processes, such as growth and reproduction. The underlying mechanisms of trade-offs between immune responses and host fitness remain poorly understood.
We used a Musca domestica mutant (pirk-KO) to evaluate the influence of non-infection-induced immune system activation on female reproduction and larval growth. Pirk, a negative feedback inhibitor of the immune deficiency (Imd) pathway expressed in intestine and fat body, was induced by bacteria. pirk loss enhanced the immune response of house flies, reflected in sustained upregulated antimicrobial peptide gene expression and improved resistance to bacterial infections. The phenotypic traits of pirk-KO house flies, including delayed larval growth, reduced the body weight, and impaired female fertility, were indicative of the adaptive costs associated with aberrant immune activation. The transcriptional heterogeneities between pirk-KO and wild-type (WT) male flies indicated the overactivation of the Imd signaling pathway, accompanied by significant metabolic adaptations to the loss of pirk. The upregulation of pivotal genes involved in glycolysis and the TCA cycle indicated an enhanced central carbon metabolism in pirk-KO. The downregulation of multiple key enzymes involved in the pentose phosphate pathway in pirk-KO flies suggests a reduction in metabolic flux through the pentose phosphate pathway, which in turn results in impaired anabolism. The collective findings indicate that the pirk-KO flies undergo metabolic reprogramming to increase ATP production as a response to excessive immune activation, rather than incorporating nutrients into cellular biomass for cell proliferation. The pirk-KO flies exhibited a significantly elevated food intake and elevated levels of free glucose, trehalose, and fructose in comparison to the WT flies. Nevertheless, the glycogen and triglyceride contents in the pirk-KO flies were observed to be slightly diminished in comparison to the WT group.
When the immune defense is activated, the flies extract more free energy to fuel the immunological deployment by increasing nutrient intake, as well as reducing resource allocation to non-essential life-history traits, primarily reproduction and growth.
病原体激活免疫系统会给宿主带来巨大的能量消耗，这可能导致资源从其他非必需的生物过程中转移，如生长和繁殖。免疫反应与宿主适应性之间权衡的潜在机制仍知之甚少。
我们使用家蝇突变体（pirk-KO）来评估非感染诱导的免疫系统激活对雌性繁殖和幼虫生长的影响。Pirk是一种在肠道和脂肪体中表达的免疫缺陷（Imd）途径的负反馈抑制剂，由细菌诱导产生。pirk缺失增强了家蝇的免疫反应，表现为抗菌肽基因表达持续上调以及对细菌感染的抵抗力提高。pirk-KO家蝇的表型特征，包括幼虫生长延迟、体重减轻和雌性生育力受损，表明与异常免疫激活相关的适应性成本。pirk-KO和野生型（WT）雄蝇之间的转录异质性表明Imd信号通路过度激活，同时伴随着对pirk缺失的显著代谢适应。参与糖酵解和三羧酸循环的关键基因上调表明pirk-KO中中心碳代谢增强。pirk-KO果蝇中参与磷酸戊糖途径的多种关键酶下调表明通过磷酸戊糖途径的代谢通量减少，进而导致合成代谢受损。这些共同发现表明，pirk-KO果蝇进行代谢重编程以增加ATP产生，作为对过度免疫激活的反应，而不是将营养物质纳入细胞生物量以进行细胞增殖。与WT果蝇相比，pirk-KO果蝇的食物摄入量显著增加，游离葡萄糖、海藻糖和果糖水平升高。然而，与WT组相比，观察到pirk-KO果蝇中的糖原和甘油三酯含量略有减少。
当免疫防御被激活时，果蝇通过增加营养摄入以及减少对非必需生活史特征（主要是繁殖和生长）的资源分配来提取更多自由能量，以支持免疫反应。
