Immunomodulatory effects of excretory/secretory compounds from <i>Contracaecum osculatum</i> larvae in a zebrafish inflammation model

Excretory/secretory (ES) compounds isolated from third-stage larvae of the anisakid nematode Contracaecum osculatum parasitizing liver of Baltic cod were investigated for effects on immune gene expression in a zebrafish LPS-induced inflammation model. ES products containing a series of proteins, of which some had enzymatic activity, were injected solely or with LPS. ES proteins alone induced up-regulation of a number of immune-related genes, but generally to a lower degree compared to LPS. When co-injected with LPS, the worm products exacerbated merely expression of five genes affecting Th1, Th2, Th17 and innate responses compared to the LPS-injected group. However, the level of overexpression decreased in an inverse dose-dependent manner. The immune regulating action of C. osculatum ES products is interpreted as an important evolutionary ability of larval parasites in the transport host which makes it less susceptible to host immune responses whereby the probability of reaching the final host is increased.本研究针对从寄生于波罗的海鳕鱼肝脏内的异尖线虫科（Anisakidae）奥氏对盲囊线虫（Contracaecum osculatum）三期幼虫中分离得到的排泄分泌（Excretory/Secretory, ES）产物，探究其在脂多糖（Lipopolysaccharide, LPS）诱导的斑马鱼炎症模型中对免疫基因表达的调控效应。将含有一系列蛋白质（部分具备酶活性）的ES产物单独注射，或与LPS联合给药至模型中。仅注射ES蛋白即可诱导多种免疫相关基因的上调，但整体上调幅度低于单纯LPS注射组。当与LPS联合注射时，与单纯LPS注射组相比，该线虫产物仅加剧了5个参与Th1、Th2、Th17及固有免疫应答的基因的表达，但该过表达水平随剂量升高呈反向剂量依赖性降低趋势。奥氏对盲囊线虫ES产物的免疫调控作用，被认为是幼虫在转运宿主体内演化出的重要适应性特征：该特征可降低宿主免疫应答对寄生虫的清除效率，进而提升其成功抵达终末宿主的概率。