Coordination of humoral immune factors dictates compatibility between Schistosoma mansoni and Biomphalaria glabrata

Abstract

Immune factors in snails of the genus <i>Biomphalaria</i> are critical for combating <i>Schistosoma mansoni</i>, 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 <i>B. glabrata</i>, and <i>S. mansoni</i>. Here, we demonstrate association between four previously characterized humoral immune molecules; <i>Bg</i>FREP3, <i>Bg</i>TEP1, <i>Bg</i>FREP2 and Biomphalysin. We also identify unique immune determinants in the plasma of <i>S. mansoni</i>-resistant <i>B. glabrata</i> that associate with the incompatible phenotype. These factors coordinate to initiate haemocyte-mediated destruction of <i>S. mansoni</i> sporocysts via production of reactive oxygen species. The inclusion of <i>Bg</i>FREP2 in a <i>Bg</i>FREP3-initiated complex that also includes <i>Bg</i>TEP1 almost completely explains resistance to <i>S. mansoni</i> 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.