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

Author summary Ascariasis is considered a major problem for the public health system, which has an estimated 800 million infected people worldwide. It occurs in the United States, Africa, Asia, and Latin America, and is generally associated with poverty and precarious health conditions. Pulmonary fibrosis affects 14-63 people per 100,000 habitants/year, and is characterized by collagen deposition and alveolar wall thickening. The comorbidities caused by infections are commonly associated with pulmonary fibrosis exacerbations, poor prognosis, and high mortality. Despite the comorbidities caused by helminth infections, which display a pulmonary parasitic cycle such as that of Ascaris, there is no evidence relating to pulmonary fibrosis progression, possibly because Ascariasis is considered a neglected disease. We evaluated the role of Ascaris during pulmonary fibrosis. We considered two simple questions: (1) Whether Ascaris infection could protect or aggravate fibrosis (comorbidities) and (2) whether pulmonary fibrosis could change the cycle of Ascaris as a result of increased alveolar thickening, larvae retention, and the limitation of influx into airways. We answered both questions as follows: (1) Ascaris infection exacerbates pulmonary and liver injury and inflammation, but not fibrosis; and (2) Pulmonary fibrosis did not alter the course of Ascaris cycle in lungs during transmigration into airways, because Ascaris preferentially seeks and penetrates into the lung areas, which are thought to be preserved, but not into fibrotic areas. 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 Ascaris suum (A. suum) 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 A. suum in mice. The most important findings related to comorbidity in which A. suum 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 A. suum 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 A. suum cycle in the lungs.