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

Abstract

Background Ascariasis and malaria are highly prevalent parasitic diseases in tropical regions and often have overlapping endemic areas, contributing to high morbidity and mortality rates in areas with poor sanitary conditions. Several studies have previously aimed to correlate the effects of Ascaris-Plasmodium coinfections but have obtained contradictory and inconclusive results. Therefore, the present study aimed to investigate parasitological and immunopathological aspects of the lung during murine experimental concomitant coinfection by Plasmodium berghei and Ascaris suum during larvae ascariasis. Methods C57BL/6J mice were inoculated with 1 × 104P. berghei strain NK65-NY-infected red blood cells (iRBCs) intraperitoneally and/or 2500 embryonated eggs of A. suum by oral gavage. P. berghei parasitaemia, morbidity and the survival rate were assessed. On the seventh day postinfection (dpi), A. suum lung burden analysis; bronchoalveolar lavage (BAL); histopathology; NAG, MPO and EPO activity measurements; haematological analysis; and respiratory mechanics analysis were 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 and TGF-β were assayed by sandwich ELISA. Results Animals coinfected with P. berghei and A. suum show decreased production of type 1, 2, and 17 and regulatory cytokines; low leukocyte recruitment in the tissue; increased cellularity in the circulation; and low levels of NAG, MPO and EPO activity that lead to an increase in larvae migration, as shown by the decrease in larvae recovered in the lung parenchyma and increase in larvae recovered in the airway. This situation leads to severe airway haemorrhage and, consequently, an impairment respiratory function that leads to high morbidity and early mortality. Conclusions This study demonstrates that the Ascaris-Plasmodium interaction is harmful to the host and suggests that this coinfection may potentiate Ascaris-associated pathology by dampening the Ascaris-specific immune response, resulting in the early death of affected animals.

N-(coumarin-3-yl)cinnamamide Promotes Immunomodulatory, Neuroprotective, and Lung Function-Preserving Effects during Severe Malaria

“…The lungs were analyzed to assess inflammation in the airway and perivascular and parenchymal regions. The score was based on a previously described method [ 65 ]. For histopathological analysis, the brain fragments were analyzed for the presence of congestion, hemorrhage areas, and cellular infiltration.…”

Helminth-host-environment interactions: Looking down from the tip of the iceberg

“…However, simultaneous infection of mice with P. berghei and Ascaris suum eggs had no impact on P. berghei parasitemia. Instead, co-infection increased lung damage and mortality and was associated with the more rapid migration of A. suum larvae through the lungs into the airways (Vieira-Santos et al 2021).…”

Ascaris Mouse Model Protocols: Advancing Research on Larval Ascariasis Biology

“…Indeed, the Ascaris mouse model (Fig. 1) has been widely utilized for studies of liver inflammation (Deslyper et al, 2019;Oliveira, Kramer, et al, 2022), type 2 immune responses in the lung tissue (Gazzinelli-Guimaraes et al, 2013;Gazzinelli-Guimaraes et al, 2019;Weatherhead et al, 2018), host genetics underlying susceptibility to infection (Dold et al, 2010;Lewis et al, 2006;, re-infections (Nogueira et al, 2016), and co-infections and interactions (Gazzinelli-Guimaraes et al, 2017;Gazzinelli-Guimaraes et al, 2019;Oliveira et al, 2019;Vieira-Santos et al, de Almeida Lopes et al…”

“…Indeed, the Ascaris mouse model (Fig. 1) has been widely utilized for studies of liver inflammation (Deslyper et al., 2019; Oliveira, Kramer, et al., 2022), type 2 immune responses in the lung tissue (Gazzinelli‐Guimaraes et al., 2013; Gazzinelli‐Guimaraes et al., 2019; Weatherhead et al., 2018), host genetics underlying susceptibility to infection (Dold et al., 2010; Lewis et al., 2006; Oliveira, Nogueira, et al., 2022), re‐infections (Nogueira et al., 2016), and co‐infections and interactions (Gazzinelli‐Guimaraes et al., 2017; Gazzinelli‐Guimaraes et al., 2019; Oliveira et al., 2019; Vieira‐Santos et al., 2021), and finally as an important tool for preclinical vaccine trials (Castro et al., 2023; Gazzinelli‐Guimaraes et al., 2018; Gazzinelli‐Guimaraes, Nogueira, et al., 2021; Wei et al., 2017), because it allows the evaluation of infection‐driven pathogenesis as well as vaccine‐driven immunogenicity at a tissue level.…”