PIWI silencing mechanism involving the retrotransposonnimbusorchestrates resistance to infection withSchistosoma mansoniin the snail vector,Biomphalaria glabrata

BackgroundSchistosomiasis remains widespread in many regions despite efforts at its elimination. By examining changes in the transcriptome at the host-pathogen interface in the snailBiomphalaria glabrataand the blood flukeSchistosoma mansoni,we previously demonstrated that an early stress response in juvenile snails, manifested by induction of heat shock protein 70 (Hsp 70) and Hsp 90 and of the reverse transcriptase (RT) domain of theB. glabratanon-LTR-retrotransposon,nimbus, were critical forB. glabratasusceptibility toS. mansoni. Subsequently, juvenileB. glabrataBS90 snails, resistant toS. mansoniat 25°C become susceptible by the F2 generation when maintained at 32°C, indicating an epigenetic response.Methodology/Principal FindingsTo better understand this plasticity in susceptibility of the BS90 snail, mRNA sequences were examined fromS. mansoniexposed juvenile BS90 snails cultured either at 25°C (permissive temperature) or 32°C (non-permissive). Comparative analysis of transcriptomes from snails cultured at the non-permissive and permissive temperatures revealed that whereas stress related transcripts dominated the transcriptome of susceptible BS90 juvenile snails at 32°C, transcripts encoding proteins with a role in epigenetics, such as PIWI (BgPiwi), chromobox protein homolog 1 (BgCBx1), histone acetyl transferase histone deacetylase (HDAC) and metallotransferase (MT) were highly expressed in those cultured at 25°C. To further determine a role forBgPiwiinB. glabratasusceptibility toS. mansoni, siRNA corresponding to theBgPiwiencoding transcript was utilized to suppress expression ofBgPiwi, rendering the resistant BS90 juvenile snail susceptible to infection at 25°C. Given transposon silencing activity of PIWI as a facet of its role as guardian of the integrity of the genome, we examined the expression of thenimbusRT encoding transcript at 120 min after infection of resistant BS90piwi-siRNA treated snails. We observed thatnimbusRT was upregulated, indicating that modulation of the transcription of thenimbusRT was associated with susceptibility toS. mansoniinBgPiwi-siRNA treated BS90 snails. Furthermore, treatment of susceptible snails with the RT inhibitor lamivudine, before exposure toS. mansoni, blockedS. mansoniinfection concurrent with downregulation of thenimbusRT transcript and upregulation of theBgPiwiencoding transcript in the lamivudine-treated, schistosome-exposed susceptible snails.Conclusions and SignificanceThese findings support a role for the interplay ofBgPiwiandnimbusin the epigenetic modulation of plasticity of resistance/susceptibility in the snail-schistosome relationship.