Department of Plant Medicals, College of Life Sciences, Andong National University, Andong 36729, Republic of Korea.
Department of SmartBio, Kyungsung University, Busan, Republic of Korea.
Pestic Biochem Physiol. 2024 Nov;205:106155. doi: 10.1016/j.pestbp.2024.106155. Epub 2024 Sep 26.
Excessive and unnecessary immune responses cause serious adverse effects due to self-tissue damage and energy consumption, particularly at the late stage of infection to terminate the induced immunity. Unlike mammals, which use long-chain fatty acid oxylipins, C18 oxygenated polyunsaturated fatty acids are suggested to act as immune resolvins in insects, including two epoxyoctadecamonoenoic acids (9,10-EpOME and 12,13-EpOME). This study investigated the physiological roles of EpOMEs in immune resolution in the lepidopteran insect, Maruca vitrata. The levels of two EpOMEs in the larvae increased during the late infection stage upon immune challenge. At their peak concentrations at 96 h post-infection (pi), both EpOMEs were found at similar levels: 323.18 pg/mg body weight for 9,10-EpOME and 322.07 pg/mg body weight for 12,13-EpOME. Both EpOMEs inhibited cellular and humoral immune responses, with 12,13-EpOME being more potent than 9,10-EpOME. Genes associated with EpOME synthase and degradation, identified as Mv-CYP1 and Mv-sEH, were detected in various developmental stages and tissues of M. vitrata. RNA interference (RNAi) targeting Mv-CYP1 failed to inhibit the immune response, whereas RNAi targeting Mv-sEH enhanced the immunosuppression. In contrast to the acute (< 12 h pi) immune response involving eicosanoid biosynthesis, the expression of these two genes linked to EpOME metabolism increased significantly at the late infection stage (> 12 h pi). Several alkoxide analogs of EpOME, with the epoxide group replaced by an alkoxide group, were synthesized; one such derivative demonstrated substantially greater efficacy than the natural EpOMEs in inhibiting the immune response. Additionally, using EpOME alkoxide significantly increased the effectiveness of microbial insecticides. Moreover, exposing young larvae to sublethal doses of EpOME alkoxide or sEH inhibitor induced severe developmental delays. These results suggest a novel strategy for insect pest control using insect immune resolvin analogs.
过量和不必要的免疫反应会导致严重的不良反应，因为它会造成自身组织损伤和能量消耗，尤其是在感染后期，需要终止诱导的免疫。与哺乳动物利用长链脂肪酸氧化产物不同，在昆虫中，C18 含氧多不饱和脂肪酸被认为是免疫消退素，包括两种环氧化物十八碳二烯酸（9,10-EpOME 和 12,13-EpOME）。本研究探讨了 EpOMEs 在鳞翅目昆虫大菜粉蝶幼虫免疫消退中的生理作用。在免疫挑战后的晚期感染阶段，幼虫体内两种 EpOMEs 的水平升高。在感染后 96 小时（pi）达到峰值浓度时，两种 EpOMEs 的水平相似：9,10-EpOME 为 323.18 pg/mg 体重，12,13-EpOME 为 322.07 pg/mg 体重。两种 EpOMEs 均抑制细胞和体液免疫反应，12,13-EpOME 的抑制作用强于 9,10-EpOME。在大菜粉蝶的不同发育阶段和组织中检测到与 EpOME 合酶和降解相关的基因，即 Mv-CYP1 和 Mv-sEH。针对 Mv-CYP1 的 RNA 干扰（RNAi）未能抑制免疫反应，而针对 Mv-sEH 的 RNAi 增强了免疫抑制作用。与涉及花生四烯酸生物合成的急性（<12 h pi）免疫反应不同，与 EpOME 代谢相关的这两个基因的表达在感染后期（>12 h pi）显著增加。合成了几种 EpOME 的烷氧基类似物，将环氧基团用烷氧基基团取代；其中一种衍生物在抑制免疫反应方面的效果明显优于天然 EpOMEs。此外，使用 EpOME 烷氧基类似物显著提高了微生物杀虫剂的效果。此外，用亚致死剂量的 EpOME 烷氧基类似物或 sEH 抑制剂处理幼龄幼虫会导致严重的发育迟缓。这些结果表明，利用昆虫免疫消退素类似物控制昆虫害虫是一种新策略。
