Comorbidity associated with Ascaris suum infection during pulmonary fibrosis exacerbates chronic lung and liver inflammation and dysfunction but does not affect the parasite cycle in mice

Ascariasis is considered the most neglected tropical disease, and is a major problem for the public health system. However, idiopathic pulmonary fibrosis (IPF) is a result of chronic extracellular deposition of matrix in the pulmonary parenchyma, and thickening of the alveolar septa, which reduces alveolar gas exchange. Considering the high rates of ascariasis and pulmonary fibrosis, we believe that these two diseases may co-exist and possibly lead to comorbidities. We therefore investigated the mechanisms involved in comorbidity of <i>Ascaris suum </i>(<i>A. suum</i>) infection, which could interfere with the progression of pulmonary fibrosis. In addition, we evaluated whether a previous lung fibrosis could interfere with the pulmonary cycle of <i>A. suum</i> in mice. The most important findings related to comorbidity in which <i>A. suum</i> infection exacerbated pulmonary and liver injury, inflammation and dysfunction, but did not promote excessive fibrosis in mice during the investigated comorbidity period. Interestingly, we found that pulmonary fibrosis did not alter the parasite cycle that transmigrated preferentially through preserved but not fibrotic areas of the lungs. Collectively, our results demonstrate that <i>A. suum</i> infection leads to comorbidity, and contributes to the aggravation of pulmonary dysfunction during pulmonary fibrosis, which also leads to significant liver injury and inflammation, without changing the <i>A. suum</i> cycle in the lungs.<br>

蛔虫病（Ascariasis）被视为最受忽视的热带疾病，亦是公共卫生体系面临的重大难题。特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）是肺实质内基质发生慢性细胞外沉积、肺泡隔增厚引发的病理改变，可降低肺泡气体交换效率。鉴于蛔虫病与肺纤维化的高患病率，我们推测二者可能共存，并有可能引发共病。为此，本研究探讨了猪蛔虫（*Ascaris suum*，简称*A. suum*）感染引发共病的相关机制，该机制或可影响肺纤维化的进展；此外，我们还评估了小鼠体内既往存在的肺纤维化是否会干扰猪蛔虫的肺部寄生周期。本研究关于共病的核心结果显示：在本次共病研究周期内，猪蛔虫感染会加重小鼠的肺部与肝脏损伤、炎症反应及功能障碍，但并未促进小鼠体内过度纤维化的发生。值得关注的是，我们观察到肺纤维化并未改变该寄生虫的迁移路径——其仍会优先穿过肺部未发生纤维化的正常区域。综上，本研究结果表明，猪蛔虫感染可引发共病，在肺纤维化进程中会加剧肺部功能障碍，同时还会造成显著的肝脏损伤与炎症反应，且不会改变猪蛔虫在肺部的寄生周期。