Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
Proc Biol Sci. 2022 Aug 31;289(1981):20220837. doi: 10.1098/rspb.2022.0837. Epub 2022 Aug 17.
The insect gut is frequently exposed to pathogenic threats and must not only clear these potential infections, but also tolerate relatively high microbe loads. In contrast to the mechanisms that eliminate pathogens, we currently know less about the mechanisms of disease tolerance. We investigated how well-described mechanisms that prevent, signal, control or repair damage during infection contribute to the phenotype of disease tolerance. We established enteric infections with the bacterial pathogen in transgenic lines of fruit flies affecting (a major component of the peritrophic matrix), (a cytokine-like molecule), (a negative regulator of reactive oxygen species) and (epithelial growth factor receptor). Flies lacking experienced the highest mortality, while loss of function of either or reduced tolerance in both sexes. The disruption of resulted in a severe loss in tolerance in male flies but had no substantial effect on the ability of female flies to tolerate infection, despite carrying greater microbe loads than males. Together, our findings provide evidence for the role of damage limitation mechanisms in disease tolerance and highlight how sexual dimorphism in these mechanisms could generate sex differences in infection outcomes.
昆虫肠道经常暴露于致病威胁之下，不仅必须清除这些潜在的感染，还必须耐受相对较高的微生物负荷。与消除病原体的机制相比，我们目前对疾病耐受的机制知之甚少。我们研究了在感染过程中防止、信号传递、控制或修复损伤的既定机制如何有助于疾病耐受表型。我们用细菌病原体 在影响 （围食膜的主要成分）、 （细胞因子样分子）、 （活性氧的负调节剂）和 （上皮生长因子受体）的 转基因品系中建立肠内感染。缺乏 的果蝇死亡率最高，而 或 功能丧失都会降低两性的耐受性。 的破坏导致雄性果蝇的耐受性严重丧失，但对雌性果蝇耐受 感染的能力没有实质性影响，尽管它们携带的微生物负荷比雄性果蝇高。总之，我们的研究结果为损伤限制机制在疾病耐受中的作用提供了证据，并强调了这些机制中的性别二态性如何产生感染结果中的性别差异。
