ConcurrentAscarisinfection modulates host immunity resulting in impaired control ofSalmonellainfection in pigs

Abstract

AbstractAscarisis 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 pathogenSalmonella,where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoingAscarisinfection on the immune response toSalmonellain pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected withSalmonellaalone.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 toSalmonellainfectionin vitro. Furthermore,AscarisimpairedSalmonella-induced monocytosis and TNF-α production by myeloid cells. Hence, our data demonstrate widespread immunomodulation during an acuteAscarisinfection that facilitates the microbial spread into gut-associated lymphoid tissue in aSalmonellacoinfection.ImportanceIn experimentally infected pigs we show that an ongoing infection with the parasitic wormAscaris suummodulates host immunity to render pigs more susceptible to invadingSalmonella.Both infections are widespread in pig production and the prevalence ofSalmonellais high in endemic regions of human Ascariasis, indicating that this is a clinically meaningful coinfection. We observed a type 2 immune response to be induced during anAscarisinfection correlating with an increased susceptibility of pigs to the concurrent bacterial infection.