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

Abstract

BackgroundWe 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).MethodsRNA-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.ResultsA 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.Conclusions1) 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.

Compatibility between snails and schistosomes: insights from new genetic resources, comparative genomics, and genetic mapping

“…This finding is partially consistent with recent studies suggesting that transmembrane proteins play a role in resistance to infections in B. glabrata 24 , 26 . Although most of genes identified in QTLs are uncharacterized or unknown in defense, we examined 49 genes from these two QTLs and found 28 are significantly upregulated in BS90 snails at 12 h post exposure to S. mansoni 57 . Functional investigations (e.g., RNAi-knockdown and/or CRISPR-mediated knockout) of these genes, especially those located at the peak of LODs, are needed.…”

Bulinus snails in the Lake Victoria Basin in Kenya: Systematics and their role as hosts for schistosomes

“…Such gastropods are often termed intermediate hosts because of their obligatory role in schistosome larval development, and although they do not directly deliver parasites to their vertebrate hosts as, for example, a mosquito transmits malaria parasites, they nonetheless play an indispensable vector role. Successful transmission of vector-borne parasites like schistosomes is dependent on a variety of factors, including ecological circumstances which impact the encounter rates between parasite and vector [6][7][8], associations with particular symbionts including those that prey on the free-living forms of certain parasites [9], facilitated susceptibility where prior infection with a specific parasite allows a second parasite to develop in a non-typical host [10,11], and nuanced physiological and immunological interactions which dictate the outcome of an infection [2,[12][13][14][15][16][17][18][19][20].…”

Single cell RNA sequencing reveals hemocyte heterogeneity in Biomphalaria glabrata: Plasticity over diversity

“…We have in this cluster active cells, with generalist functions of cell maintenance but also cells able to express marker genes already described in the literature. Indeed, we found however several Pattern Recognition Receptors (PRRs) that can recognize different types of pathogens, and some of which have a very important role in immunity against S. mansoni parasite and especially in the recognition of this parasite, such as FREPs ( 45 ), MAM and LDL-receptor class A domain-containing 1-like ( 46 ) or genes containing von Willebrand factor EGF and pentraxin domain-containing 1 ( 47 ) that have been described in other models and which could have a role in suppressing or modulating the immunity ( Supplementary Table 2 ). We proposed that cluster 0, named latent hemocytes ( Figure 1F ), is composed of circulating hemocytes that are waiting for activation in the case of a potential encounter and infection with a pathogen or the activation of alarmins.…”