Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

Abstract

It is long known that some parasite infections are able to modulate specific pathways of host's metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases.

Praziquantel treatment after Schistosoma japonicum infection maintains hepatic insulin sensitivity and improves glucose metabolism in mice

“…Infections with certain helminths such as Schistosoma mansoni and Necator americanus , and protozoan parasites such as Leishmania and Toxoplasma [ 18 ], and their excretory/secretory products can manipulate host immune responses toward a Th2 immune phenotype. Emerging data suggests that helminths may help protect against MetS as well as autoimmune and allergic diseases [ 19 , 20 ]. In studies on obese mice [ 11 , 21 ], chronic infection with S. mansoni and treatment with SEA or immunomodulatory glycan LNFPIII, which is found in SEA, alleviated both hepatosteatosis and insulin resistance [ 11 ].…”

Schistosoma mansoni SmKI-1 serine protease inhibitor binds to elastase and impairs neutrophil function and inflammation

“…Many studies reveal that schistosomes down-regulate inflammatory responses in immune-mediated diseases [ 9 – 12 ]. Fortunately, the control of inflammation seems not to be strictly dependent on parasite infection, since it is extended to some pathogen-derived antigens [ 9 , 11 , 12 ], suggesting some schistosome molecules are useful weapons to control inflammation [ 13 , 14 ].…”

Maternal Schistosomiasis: Immunomodulatory Effects With Lasting Impact on Allergy and Vaccine Responses

“…Much of the epidemiological impact of helminth infections with strong immunomodulatory effects has been extensively reviewed in Feary et al (5), Janssen et al (6), Wammes et al (7), including the range of effects that Schistosoma mansoni infection, or exposure to its released products, live or dead eggs, soluble egg antigen (SEA) extracts, or even recombinantly expressed schistosome-derived proteins have upon inflammatory and autoimmune diseases. This current review instead aims to place these and more recent findings within the context of perturbations during immune ontogenesis, where much research has thus far focused on bacterial and viral infections.…”