Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice

Toxocariasis is a neglected disease caused by <i>Toxocara canis</i>, which has 19% worldwide seroprevalence, and is associated with socioeconomic, geographic and environmental factors. Humans become infected by accidental ingestion of <i>T. canis</i> eggs present in contaminated food, water or soil. After ingestion, the larvae hatch in the intestine and can reach various tissues such as liver, lung and brain. Helminth infections usually trigger a Th2 immune response in the host, by releasing cytokines such as IL-4, IL-5, IL-13 and IL-33. IL-33 is an alarmin that binds to the ST2 receptor, and some studies have observed an increase in this cytokine in toxocariasis, however there are no studies regarding the IL-33/ST2 role in this infection. Thus, we evaluated the influence of this pathway by analyzing immunological and pathophysiological aspects in <i>T. canis</i>-infected mice. Our results demonstrated that the IL-33/ST2 pathway is related to parasite burden on the liver and brain and also increases the number of eosinophils in the blood and tissues. In addition, it involved with the pulmonary immune response and granulomas with impact in lung function. In conclusion, the IL-33/ST2 pathway governs the host susceptibility to <i>T. canis </i>in mice.<br>

弓首蛔虫病（Toxocariasis）是一种被忽视的疾病，由犬弓首蛔虫（Toxocara canis）引起，全球血清阳性率达19%，其发病与社会经济、地理及环境因素密切相关。人类因意外摄入受污染食物、水或土壤中的犬弓首蛔虫虫卵而感染。摄入虫卵后，幼虫在肠道内孵化，并可迁移至肝脏、肺脏、大脑等多种组织。蠕虫感染通常会通过释放IL-4、IL-5、IL-13及IL-33等细胞因子，触发宿主的Th2型免疫应答。IL-33是一种结合ST2受体的警报素，已有研究观察到弓首蛔虫病患者体内该细胞因子水平升高，但目前尚无关于IL-33/ST2通路在该感染中作用的相关研究。因此，本研究通过分析犬弓首蛔虫感染小鼠的免疫学及病理生理学特征，评估了该通路的影响。研究结果显示，IL-33/ST2通路与肝脏及大脑内的寄生虫负荷相关，同时可升高血液与组织中的嗜酸性粒细胞数量。此外，该通路还参与肺部免疫应答及肉芽肿形成，进而对肺功能产生影响。综上，在小鼠模型中，IL-33/ST2通路决定了宿主对犬弓首蛔虫感染的易感性。