C-type lectin receptor signaling in schistosomiasis.

Schistosomiasis is a major neglected tropical disease caused by helminth parasites of the genus Schistosoma, affecting over 250 million people worldwide and leading to substantial morbidity primarily driven by egg-induced immunopathology. Schistosome parasite can modulate host immunity through stage-specific glycans displayed on cercariae, schistosomula, adult worms, and eggs. These glycans form a critical molecular interface with host C-type lectin receptors (CLRs), a family of carbohydrate-recognition receptors predominantly expressed by dendritic cells, macrophages, and other innate immune cells. CLRs recognize schistosome-derived glycoproteins and glycolipids through C-type lectin-like domains and translate extracellular glycan sensing into intracellular signaling pathways that shape downstream immune responses. Emerging evidence demonstrates that key CLRs, including the mannose receptor, DC-SIGN, MGL, MBL, Dectin-1, Dectin-2, and Mincle, play distinct and sometimes opposing roles during schistosomiasis by regulating antigen uptake, cytokine production, inflammasome activation, and T-helper cell differentiation. Depending on receptor engagement, CLR signaling can promote protective Th2 immunity, drive pathogenic Th17 responses associated with severe hepatic fibrosis, or induce regulatory pathways that limit excessive inflammation. Moreover, CLR-mediated signaling does not occur in isolation but involves extensive crosstalk with other pattern recognition receptors, particularly Toll-like receptors. Despite significant progress, critical gaps remain in understanding receptor specificity, context-dependent signaling, and the role of CLRs in disease susceptibility. This review synthesizes current knowledge on CLR-schistosome interactions, highlighting their central role in immune modulation and disease pathogenesis.