Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Sci Rep. 2020 May 13;10(1):7901. doi: 10.1038/s41598-020-64788-6.
Schistosomiasis is a human parasitic disease responsible for serious consequences for public health, as well as severe socioeconomic impacts in developing countries. Here, we provide evidence that the adaptor molecule STING plays an important role in Schistosoma mansoni infection. S. mansoni DNA is sensed by cGAS leading to STING activation in murine embryonic fibroblasts (MEFs). Sting and C57BL/6 (WT) mice were infected with schistosome cercariae in order to assess parasite burden and liver pathology. Sting mice showed worm burden reduction but no change in the number of eggs or granuloma numbers and area when compared to WT animals. Immunologically, a significant increase in IFN-γ production by the spleen cells was observed in Sting animals. Surprisingly, Sting mice presented an elevated percentage of neutrophils in lungs, bronchoalveolar lavage, and spleens. Moreover, Sting neutrophils exhibited increased survival rate, but similar ability to kill schistosomula in vitro when stimulated with IFN-γ when compared to WT cells. Finally, microbiota composition was altered in Sting mice, revealing a more inflammatory profile when compared to WT animals. In conclusion, this study demonstrates that STING signaling pathway is important for S. mansoni DNA sensing and the lack of this adaptor molecule leads to enhanced resistance to infection.
曼氏血吸虫病是一种人类寄生虫病，对公共卫生造成严重后果，并给发展中国家造成严重的社会经济影响。在这里，我们提供的证据表明衔接分子 STING 在曼氏血吸虫感染中发挥重要作用。cGAS 可检测到曼氏血吸虫 DNA，从而导致鼠胚胎成纤维细胞（MEFs）中 STING 的激活。用曼氏血吸虫尾蚴感染 Sting 和 C57BL/6（WT）小鼠，以评估寄生虫负荷和肝脏病理学。与 WT 动物相比，Sting 小鼠的蠕虫负荷减少，但卵的数量或肉芽肿的数量和面积没有变化。免疫方面，Sting 动物的脾细胞产生 IFN-γ 的数量显著增加。令人惊讶的是，Sting 小鼠的肺部、支气管肺泡灌洗液和脾脏中的中性粒细胞百分比升高。此外，与 WT 细胞相比，当用 IFN-γ 刺激时，Sting 中性粒细胞的存活率增加，但杀死曼氏血吸虫尾蚴的能力相似。最后，Sting 小鼠的微生物群组成发生改变，与 WT 动物相比表现出更具炎症特征。总之，这项研究表明，STING 信号通路对 S. mansoni DNA 的检测很重要，缺乏这种衔接分子会导致对感染的抵抗力增强。
