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

Human ascariasis is a widespread and overlooked disease, affecting approximately 446 million people worldwide, making it the most prevalent geohelminthiasis globally. In regions with endemic prevalence, recurrent infections are frequent, attributed to inadequate sanitation and ineffective health education. In this scenario, most infected adults are exposed to the parasite multiple times and have a low parasite burden. Further evaluations are necessary to provide more evidence on infection dynamics, especially in the acute phase. An essential investigation involves comparing the impact on pulmonary function between single and multiple infections in a murine model. The emphasis should be on unraveling potential mechanisms that contribute to the regulation of protection against larval ascariasis. 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. 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. Thus, the RE 250 group exhibited a decrease of parasite burden close to RE 2500, but with less tissue damage. As a result, it displayed the most favorable prognosis among the reinfected groups. Additionally, a dose-dependent relationship was identified between the production of antibodies and the intensity of the immune response needed to regulate the parasite burden.