An Overview of Transcriptional Responses of Schistosome-Susceptible (M line) or -Resistant (BS-90) Biomphalaria glabrata Exposed or Not to Schistosoma mansoni Infection

Abstract

Background: We seek to provide a comprehensive overview of transcriptomics responses of immune-related features of the gastropod Biomphalaria glabrata (Bg) following exposure to Schistosoma mansoni (Sm), a trematode causing human schistosomiasis. Responses of schistosome-susceptible (M line, or SUS) and -resistant (BS-90, or RES) Bg strains were characterized following exposure to Sm for 0.5, 2, 8 or 40 days post-exposure (dpe).

Methods: RNA-Seq and differential expression analysis were undertaken on 56 snails from 14 groups. We considered 7 response categories: 1) constitutive resistance factors; 2) constitutive susceptibility factors; 3) generalized stress responses; 4) induced resistance factors; 5) resistance factors suppressed in SUS snails; 6) suppressed/manipulated factors in SUS snails; and 7) tolerance responses in SUS snails. We also undertook a gene co-expression network analysis. Results from prior studies identifying schistosome resistance/susceptibility factors were examined relative to our findings.

Results: A total of 792 million paired-end reads representing 91.2% of the estimated 31,985 genes in the Bg genome were detected and results for the 7 categories compiled and highlighted. For both RES and SUS snails, a single most supported network of genes with highly correlated expression was found.

Conclusions: 1) Several constitutive differences in gene expression between SUS and RES snails were noted, the majority over-represented in RES; 2) There was little indication of a generalized stress response shared by SUS and RES snails at 0.5 or 2 dpe; 3) RES snails mounted a strong, multi-faceted response by 0.5 dpe that carried over to 2 dpe; 4) The most notable SUS responses were at 40 dpe, in snails shedding cercariae, when numerous features were either strongly down-regulated indicative of physiological distress or parasite manipulation, or up-regulated, suggestive of tolerance or survival-promoting effects; 5) Of 55 genes previously identified in genome wide mapping studies, 29 (52.7%) were responsive to Sm, as were many familiar resistance-associated genes (41.0%) identified by other means; 6) Both network analysis and remarkably specific patterns of expression of lectins and G protein-coupled receptors in categories 4, 6 and 7 were indicative of orchestrated responses of different suites of genes in SUS or RES snails following exposure to Sm.

Keywords: Biomphalaria glabrata; RNA-sequencing; Schistosoma mansoni; comparative immunology; schistosomiasis; transcriptomics; vector biology.