Concurrent Ascaris infection modulates host immunity resulting in impaired control of Salmonella infection in pigs

Ascaris is one of the most widespread helminth infections of humans and pigs, leading to chronic morbidity in humans and considerable economic losses in pig farming. Additionally, pigs are an important reservoir for the zoonotic bacterial pathogen Salmonella, where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoing Ascaris infection on the immune response to Salmonella in pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected with Salmonella alone. Ascaris- infected pigs exhibited numerous hallmarks of a type 2 immune response in organs impacted by larval migration, including increased Th2 cells, increased IL-4 production, eosinophilia, and increased expression of CD206, a marker for alternatively activated macrophages. While we observed only mild changes in frequencies of CD4 ⁺ Treg, Ascaris- infected pigs had increased frequencies of CD8α ⁺ Treg. We show that type 2 immune signals enhance susceptibility of macrophages to Salmonella infection in vitro . Furthermore, Ascaris impaired Salmonella- induced monocytosis and TNF-α production by myeloid cells. Hence, our data demonstrate widespread immunomodulation during an acute Ascaris infection that facilitates the microbial spread into gut-associated lymphoid tissue in a Salmonella coinfection.