Dectin-1 Induces Severe Th17 Cell- Mediated Schistosome Immunopathology
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Santoshi Chaudhary
Exhibition Number 109
Abstract
Schistosomiasis is the second most prevalent parasitic disease, affecting approximately 251 million people worldwide. Schistosoma mansoni is a major causative agent of this disease, and treatment relies solely on Praziquantel. However, this increases the risk of reinfection and potential parasite resistance. Thus, further research is needed to better understand disease pathogenesis and identify alternative therapeutic targets. C-type lectin receptors (CLRs) play a crucial role in pathogen recognition due to the glycan-rich nature of Schistosoma eggs and adult worms. Dectin-1, a CLR known for its antifungal role through -glucan recognition, may also influence the immune response during schistosomiasis. However, its role in schistosomiasis remains unclear. Therefore, the objective of the study is to investigate the role of Dectin-1 in the immune response during Schistosoma mansoni infection. To investigate this, we infected C57BL/6 and Dectin-1 knockout (KO) mice with 80 S. mansoni cercariae and after seven weeks, harvested the liver, spleen, mesenteric lymph nodes, and intestines for analysis. Bone marrow-derived dendritic cells (BMDCs) from C57BL/6 and Dectin-1 KO were stimulated with live eggs to assess cytokine production and RNA sequencing. Dectin-1 KO mice exhibited lower liver and spleen masses and reduced egg-induced hepatic immunopathology, as evidenced by smaller granulomas compared to wild-type mice. Furthermore, Dectin-1 promoted proinflammatory cytokines (IL-1, IL-17) while inhibiting the anti-inflammatory cytokine IL-10. RNA sequencing revealed downregulation of proinflammatory genes (IL-12a, IFN-, IL-1, IL-6), inflammasome (NLRP3), and cell surface receptors (Clec9a, TLR2) in Dectin-1 KO mice. These findings suggest that Dectin-1 has a proinflammatory role in S. mansoni infection.
Importance
Schistosomiasis affects over 250 million people worldwide, with limited treatment options relying solely on Praziquantel, which only targets adult worms and raises concerns about reinfection and drug resistance. Understanding the immune response during Schistosoma mansoni infection is crucial for identifying new therapeutic targets. This study reveals that Dectin-1, a receptor known for recognizing fungal components, also drives proinflammatory responses in S. mansoni infection. By uncovering Dectin-1’s role in promoting inflammation and regulating key cytokines, our findings highlight a potential target for modulating immune responses. These insights could pave the way for novel strategies to mitigate schistosomiasis-associated pathology, addressing an alternative therapy.