Data_Sheet_1_Host Defense Versus Immunosuppression: Unisexual Infection With Male or Female Schistosoma mansoni Differentially Impacts the Immune Response Against Invading Cercariae.docx

Infection with the intravascular diecious trematode Schistosoma spp. remains a serious tropical disease and public health problem in the developing world, affecting over 258 million people worldwide. During chronic Schistosoma mansoni infection, complex immune responses to tissue-entrapped parasite eggs provoke granulomatous inflammation which leads to serious damage of the liver and intestine. The suppression of protective host immune mechanisms by helminths promotes parasite survival and benefits the host by reducing tissue damage. However, immune-suppressive cytokines may reduce vaccine-induced immune responses. By combining a single-sex infection system with a murine air pouch model, we were able to demonstrate that male and female schistosomes play opposing roles in modulating the host’s immune response. Female schistosomes suppress early innate immune responses to invading cercariae in the skin and upregulate anergy-associated genes. In contrast, male schistosomes trigger strong innate immune reactions which lead to a reduction in worm and egg burden in the liver. Our data suggest that the female worm is a neglected player in the dampening of the host’s immune defense system and is therefore a promising target for new immune modulatory therapies.

感染间质性血吸虫（Schistosoma spp.）这一内血管寄生虫，在发展中国家依然是一种严重的热带疾病和公共卫生问题，全球范围内影响超过2.58亿人。在慢性曼氏血吸虫感染过程中，对组织内寄生虫卵的复杂免疫反应引发肉芽肿性炎症，导致肝脏和肠道的严重损伤。寄生虫通过抑制宿主保护性免疫机制来促进其生存，并通过对组织损伤的减少而使宿主受益。然而，免疫抑制性细胞因子可能降低疫苗诱导的免疫反应。通过结合单性别感染系统和小鼠气腔模型，我们得以证实雌性和雄性血吸虫在调节宿主免疫反应方面发挥着相反的作用。雌性血吸虫抑制皮肤中入侵性毛蚴的早期先天免疫反应，并上调与无反应性相关的基因。相反，雄性血吸虫触发强烈的先天免疫反应，导致肝脏和肠道中虫体和虫卵负荷的减少。我们的数据表明，雌性虫体在抑制宿主免疫防御系统方面是一个被忽视的角色，因此是新型免疫调节疗法的潜在靶点。