Concomitant experimental coinfection by Plasmodium berghei NK65-NY and Ascaris suum downregulates the Ascaris-specific immune response and potentiates Ascaris-associated lung pathology

Background: Ascariasis and malaria are highly prevalent parasitic diseases in tropical regions and often overlap in endemic areas, contributing to high morbidity and mortality rates in areas with poor sanitary conditions. Several studies have already aimed to correlate the effects of Ascaris-Plasmodium coinfections but obtained contradictory and inconclusive results. The present study investigated parasitological and immunopathological aspects of the lung in an experimental concomitant coinfection by Plasmodium berghei NK65-NY and Ascaris suum during larval ascariasis. Methods: C57BL/6J mice were inoculated with 1×104 P. berghei NK65-NY infected red blood cells (iRBCs) intraperitoneally and/or 2500 embryonated eggs of A. suum by oral gavage. P. berghei NK65-NY parasitemia, morbidity and survival rate were assessed. At the seventh day postinfection (dpi), A. suum lung burden, bronchoalveolar lavage (BAL), lung histopathological, lung cellular activity, hematological analysis and respiratory mechanics was performed. The concentrations of interleukin (IL)-1β, IL-12/IL-23p40, IL-6, IL-4, IL-33, IL-13, IL-5, IL-10, IL-17A, IFN-γ, TNF-α and TGF-β were assayed by sandwich ELISA. Results: P. berghei NK65-NY and A. suum coinfection results in Plasmodium-driven downregulation of the lung immune response that leads to an increase in larval migration, as evidenced by the decrease in larvae recovered in the lung parenchyma and increase in larvae recovered in the airways. This scenario conveys an intense airways hemorrhage and, consequently, the commitment of respiratory function that leads to high morbidity and early mortality. Conclusions: Our results suggest that this coinfection may potentiate Ascaris-associated pathology by the downmodulation of the Ascaris-specific immune response, resulting in the early death of affected animals.