Siglec homologs interact with membrane-bound Heat Shock Protein 70 (Hsp70) during early infection of the Schistosoma mansoni susceptible (BB02) Biomphalaria glabrata snail host.

Sialic acid-binding immunoglobulin-like lectins (siglecs) are cell surface receptors involved in immune signaling. When Schistosoma mansoni infects its intermediate host, the Biomphalaria glabrata snail, early stress responses, such as upregulation of heat shock protein 70 (Hsp70) are observed. We hypothesized that stress-induced Hsp70 translocates to the cell membrane and interacts with siglec homologs to modulate immune responses in the snail. Utilizing in-silico approaches, we identified B. glabrata transcripts homologous to human and molluscan siglecs, followed by homology modeling and molecular docking, which predicted a salt bridge between glutamic acid 479 on BgHsp70 and lysine 47 on a siglec homolog (BgPrx), suggesting a plausible binding interface. To validate this, we performed real-time qPCR from infected susceptible juvenile BB02 snails, revealing significant upregulation of siglec homolog transcripts shortly after infection. Additionally, protein fractionation and immunocytochemistry confirmed BgHsp70 localization to the membrane post-infection. These results support a model in which siglec-Hsp70 interactions may dampen stress signaling to suppress host immune defenses. Concurrently, S. mansoni employs glycan mimicry, presenting host-like sialylated structures that likely engage siglecs and further misdirect the immune response. Together, our findings suggest that BgHsp70-siglec interactions, in combination with parasite glycan mimicry, constitute a potential immune evasion mechanism enabling schistosome establishment in susceptible B. glabrata snails.