Schistosome Eggs Impair Protective Th1/Th17 Immune Responses Against Salmonella Infection

Abstract

Countries with a high incidence of helminth infections are characterized by high morbidity and mortality to infections with intracellular pathogens such as Salmonella. Some patients with Salmonella-Schistosoma co-infections develop a so-called “chronic septicemic salmonellosis,” with prolonged fever and enlargement of the liver and spleen. These effects are most likely due to the overall immunoregulatory activities of schistosomes such as induction of Tregs, Bregs, alternatively activated macrophages, and degradation of antibodies. However, detailed underlying mechanisms are not very well investigated. Here, we show that intraperitoneal application of live Schistosoma mansoni eggs prior to infection with Salmonella Typhimurium in mice leads to an impairment of IFN-γ and IL-17 responses together with a higher bacterial load compared to Salmonella infection alone. S. mansoni eggs were found in granulomas in the visceral peritoneum attached to the colon. Immunohistological staining revealed IPSE/alpha-1, a glycoprotein secreted from live schistosome eggs, and recruited basophils around the eggs. Noteworthy, IPSE/alpha-1 is known to trigger IL-4 and IL-13 release from basophils which in turn is known to suppress Th1/Th17 responses. Therefore, our data support a mechanism of how schistosomes impair a protective immune response against Salmonella infection and increase our understanding of helminth-bacterial co-infections.

Impaired host resistance to Salmonella during helminth co-infection is restored by anthelmintic treatment prior to bacterial challenge

“…Our current understanding of helminth-bacterial co-infections lacks information on the mechanism(s) by which certain pathogenic bacteria acquire a colonization advantage during helminth infection. Some studies have attributed this to the ability of helminths to modulate immune responses that lower host defense to other bacterial pathogens [ 9 , 12 , 14 , 16 , 17 ]. Another possible mechanism by which helminths can promote bacterial infection is through shifts in the gut metabolic environment.…”

Schistosoma mansoni Eggs Modulate the Timing of Granuloma Formation to Promote Transmission

“…SEA was prepared by Dr Gabriele Schramm. Briefly, eggs were isolated from S. mansoni -infected hamsters as previously described ( Schramm et al., 2018 ), and then homogenized in PBS, pH 7.5, using a sterile glass homogenizer. The homogenate was then centrifuged at 21 krcf for 20 min.…”

Schistosoma mansoni immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs)

“…The secretion of antigens by helminth parasites may inhibit endotoxin-induced inflammation to dampen Th1-type responses and indirectly promote a Th2 environment in which endoparasitic helminths can thrive [61][62][63]. However, the immune system modulation/polarisation exerted by flatworms and other helminth infections can leave hosts more susceptible to secondary infections that could potentially be deleterious for both the host and parasite [64][65][66]. We have suggested that dampening classical immune activation by endotoxin with secreted molecules could be a mechanism employed by trematodes like F. hepatica and S. mansoni to confer tolerance to secondary bacterial infections [67].…”