Coordination of humoral immune factors dictates compatibility between and .

Immune factors in snails of the genus are critical for combating , the predominant cause of human intestinal schistosomiasis. Independently, many of these factors play an important role in, but do not fully define, the compatibility between the model snail , and . Here, we demonstrate association between four previously characterized humoral immune molecules; FREP3, TEP1, FREP2 and Biomphalysin. We also identify unique immune determinants in the plasma of -resistant that associate with the incompatible phenotype. These factors coordinate to initiate haemocyte-mediated destruction of sporocysts via production of reactive oxygen species. The inclusion of FREP2 in a FREP3-initiated complex that also includes TEP1 almost completely explains resistance to in this model. Our study unifies many independent lines of investigation to provide a more comprehensive understanding of the snail immune system in the context of infection by this important human parasite.