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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The freshwater gastropod\n                      <jats:italic>Biomphalaria glabrata<\/jats:italic>\n                      is the major intermediate host of\n                      <jats:italic>Schistosoma mansoni<\/jats:italic>\n                      , the causative agent of human schistosomiasis. Elucidating the molecular basis of snail resistance to schistosomes is essential for understanding invertebrate immunity, host\u2013parasite interactions, and schistosomiasis epidemiology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two new\n                      <jats:italic>B. glabrata<\/jats:italic>\n                      \u2013\n                      <jats:italic>S. mansoni<\/jats:italic>\n                      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\n                      <jats:italic>S. mansoni<\/jats:italic>\n                      . Differential gene expression and gene co-expression network analyses identified constitutive and schistosome-induced genes and resistance-associated networks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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,\n                      <jats:italic>Helix pomatia<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This systems-level comparative analysis of two models with four genetically distinct\n                      <jats:italic>B. glabrata<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1949258","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:26:30Z","timestamp":1789446390000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A systems-level analysis of global gene expression in resistant and susceptible Biomphalaria glabrata in response to Schistosoma mansoni infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Abdelmalek","family":"Lekired","sequence":"first","affiliation":[{"name":"Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico","place":["Albuquerque, NM, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen 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