A systems-level analysis of global gene expression in resistant and susceptible Biomphalaria glabrata in response to Schistosoma mansoni infection.

BACKGROUND: The freshwater gastropod Biomphalaria glabrata is the major intermediate host of Schistosoma mansoni, the causative agent of human schistosomiasis. Elucidating the molecular basis of snail resistance to schistosomes is essential for understanding invertebrate immunity, host-parasite interactions, and schistosomiasis epidemiology.

METHODS: Two new B. glabrata-S. mansoni interaction models were examined: homozygous lines (HZLs) iBS90_R (resistant) and iM line_S (susceptible), and recombinant inbred lines (RILs) RIL18_R (resistant) and RIL108_S (susceptible). Snail transcriptomes were analyzed using RNA sequencing (RNAseq) data from unexposed controls and at 6, 24, and 48 hours post-exposure (hpe) to S. mansoni. Differential gene expression and gene co-expression network analyses identified constitutive and schistosome-induced genes and resistance-associated networks.

RESULTS: Each snail line exhibited a different basal transcriptional profile, including immune genes involved in parasite recognition and defense, such as genes encoding lectins, variable immunoglobulin and lectin domain-containing proteins (VIgLs) including fibrinogen-related proteins (FREPs), fibrinogen domain-containing proteins (FReDs), avrRpt2-induced gene products (AIGs), and GTPase immunity-associated proteins (GiMAPs). Resistant lines showed higher constitutive expression of some candidate defense genes, including biomphalysin, Helix pomatia agglutinin-related proteins (HREPs), nitric oxide synthase, peptidoglycan recognition protein (PGRP), and aranetoxin. Following infection, susceptible lines mounted weak early responses but underwent extensive transcriptional changes at 48 hpe, including down-regulation of multiple anti-schistosome immune genes. In contrast, resistant lines maintained robust transcriptional activation throughout infection. Although both resistant lines induced similar immune gene families, including biomphalysins, AIGs, thioester-containing proteins (TEPs), and FREPs, they shared few identical differentially expressed genes. Only three genes encoding a perlucin-like C-type lectin (PLL), a multiple epidermal growth factor (EGF)-containing protein, and a GiMAP were consistently up-regulated across all time points in both resistant lines. Co-expression network analysis indicated that resistant snails with distinct genetic backgrounds employ few shared but predominantly lineage-specific immune pathways, highlighting the complexity of host-parasite interactions.

CONCLUSIONS: This systems-level comparative analysis of two models with four genetically distinct B. glabrata lines provides novel insights into the relationships among genotype, phenotype, and gene regulation involved in the anti-schistosome response. These findings yield a valuable transcriptomic resource for dissecting resistance mechanisms and advancing understanding of invertebrate immunity.