Investigating the host immune responses to Schistosoma mansoni cercaria in acute schistosomiasis
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Megan Nitchman
Exhibition Number 69
Abstract
Schistosomiasis is a prevalent tropical parasitic disease caused partly by the helminthic parasite Schistosoma mansoni (S. mansoni) affecting more than 250 million people globally. Some patients house chronic infection with minimal symptomology; however, 5-10% present with severe immunopathology. In the context of established infection, eggs are highly inflammatory and result in hepatic granulomas, whereas adult worms are immunosuppressive and allow parasitic survival in the host if left untreated. Currently, there is no consensus as to whether the cercaria are inflammatory or immunosuppressive during invasion. Cercaria are the only life stage that is infectious to mammalian hosts. Thus, this stage has the potential for therapeutic implications by which disease severity can be reduced. We hypothesized that recognition of cercarial components by PRRs on immune cells dictates the host cellular immune response. We found that the insoluble cercarial material most strongly elicits an IL-1 dominant pro-inflammatory response mediated by C-type lectin receptor Dectin-1 in macrophages. Additionally, it was determined that inflammasome-related genes are upregulated in response to cercarial components. Together, we conclude cercaria elicit proinflammatory responses from the host via Dectin-1-mediated inflammasome priming and activation.
Importance
Schistosomiasis is a neglected tropical parasitic disease affecting more than 250 million people, largely in impoverished areas. Schistosoma mansoni (S. mansoni) is the causative species that is the most pathogenic and makes up a majority of cases. Up to 10% of patients have a severe infection which can lead to death. The immunological effects of S. mansoni on the mammalian host are not well characterized, thus Schistosomiasis rarely makes the global health agenda for pharmaceutical research. One treatment exists, praziquantel, for which parasitic resistance and reinfection rates increase. Our work aims to find new targets and elucidate the novel molecular mechanisms by which severe immunopathology is elicited such that new treatments can be developed to reduce disease severity.