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