Dose-response effects of multiple Ascaris suum exposures and their impact on lung protection during larval ascariasis

Background: Human ascariasis is the most prevalent geohelminthiasis worldwide, affecting approximately 446 million individuals. In regions with endemic prevalence, the majority of infected adults are frequently exposed to the parasite and tend to have a low parasite load. Further studies are necessary to provide more evidence on the dynamics of infection and to elucidate the possible mechanisms involved in regulating protection, especially during the acute phase, also known as larval ascariasis. The aim of this study is to compare the impact of lung function between single and multiple infections in a murine model. Methods: We infected BALB/c mice considering the frequency of exposures: single-exposure—SI; twice-exposures—RE 2x and thrice-exposures—RE 3x, and considering the doses of infection: 25 eggs—RE 25; 250 eggs—RE 250 and 2,500 eggs—RE 2500, followed by infection challenge with 2,500 eggs. From this, we evaluated: parasite burden in lungs, cellular and humoral response, histopathological and physiological alterations in lungs. Results: The main results showed a reduction of parasite burden in the reinfected groups compared to the single-infected group, with protection increasing with higher exposure and dose. Furthermore, the RE 250 group exhibited a decrease of parasite burden close to RE 2500, but with less tissue damage, displaying the most favorable prognosis among the reinfected groups. Conclusion: Our research indicates a dose-dependent relationship between antibody production and the intensity of the immune response required to regulate the parasite burden. Author summary: Human ascariasis is a common and neglected disease and is the most prevalent geohelminthiasis worldwide. In certain regions considered endemic, recurrent infections are frequent. This is mainly due to inadequate sanitation infrastructure and ineffective health education. This study aims to better understand the dynamics of Ascaris infection and thus elucidate the possible mechanisms involved in the regulation of protection, especially during the acute phase, also known as larval ascariasis. To this end, we infected BALB/c mice with different frequencies of exposure and different doses of infection. We observed a reduction in larval recovery in the re-infected groups compared to the single-infection group. This protection increased with increasing exposure frequency and dose. In addition, we found that the production of antibodies and the intensity of the immune response appeared to be related to the regulation of parasite burden.