Graduate Research Assistant Pennsylvania State University State College, Pennsylvania, United States
Disclosure(s):
Santoshi Chaudhary, PhD: No financial relationships to disclose
Introduction/Rationale: Schistosomiasis is the second most prevalent parasitic disease, affecting over 250 million people worldwide. Schistosoma mansoni is a major causative agent, and current treatment relies solely on Praziquantel, raising concerns about reinfection and potential parasite resistance. Thus, further research is needed to better understand disease pathogenesis and identify alternative therapeutic targets. Given the glycan-rich nature of Schistosoma eggs and adult worms, C-type lectin receptors (CLRs) likely play a crucial role in pathogen recognition. Dectin-1, a CLR known for its role in fungal infections, may also regulate the immune response to S. mansoni infection, though its role remains unclear. We hypothesized that Dectin-1 contributes to inflammation during S. mansoni infection.
Methods: To investigate this, C57BL/6 and Dectin-1 knockout (KO) mice were infected with 80 S. mansoni cercariae via intraperitoneal injection, and after seven weeks, livers, spleens, mesenteric lymph nodes, and intestines were harvested for pathological and immunological analysis. Bone marrow-derived dendritic cells (BMDCs) from both genotypes were stimulated with live eggs to assess cytokine production and signaling pathways.
Results: 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. Moreover, Dectin-1 promoted the production of proinflammatory cytokines IL-1β and Th17 cell responses while suppressing the anti-inflammatory cytokine IL-10. Mechanistically, Raf-1 and NF-κB were identified as downstream mediators of Dectin-1 signaling in cytokine induction.
Conclusion: Our findings suggest that Dectin-1 decisively influences the course of the schistosome infection.
