{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:20Z","timestamp":1753891160575,"version":"3.41.2"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Gnathostomiasis is an important zoonosis in tropical areas that is mainly caused by third-stage <jats:italic>Gnathostoma spinigerum<\/jats:italic> larvae (<jats:italic>G. spinigerum<\/jats:italic> L3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aimed to prove whether <jats:italic>G. spinigerum<\/jats:italic> L3 produces extracellular vesicles (EVs) and investigate human gene profiles related to the immune response against the larvae.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We created an immune cell model using normal human peripheral blood mononuclear cells (PBMCs) co-cultured with the larvae for 1 and 3 days, respectively. The PBMCs were harvested for transcriptome sequencing analysis. The EV ultrastructure was examined in the larvae and the cultured medium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Extracellular vesicle-like particles were observed under the larval teguments and in the pellets in the medium. RNA-seq analysis revealed that 2,847 and 3,118 genes were significantly expressed on days 1 and 3 after culture, respectively. The downregulated genes on day 1 after culture were involved in pro-inflammatory cytokines, the complement system and apoptosis, whereas those on day 3 were involved in T cell-dependent B cell activation and wound healing. Significantly upregulated genes related to cell proliferation, activation and development, as well as cytotoxicity, were observed on day 1, and genes regulating T cell maturation, granulocyte function, nuclear factor-\u03baB and toll-like receptor pathways were predominantly observed on day 3 after culture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>G. spinigerum<\/jats:italic> L3 produces EV-like particles and releases them into the excretory-secretory products. Overall, genotypic findings during our 3-day observation revealed that most significant gene expressions were related to T and B cell signalling, driving T helper 2 cells related to chronic infection, immune evasion of the larvae, and the pathogenesis of gnathostomiasis. Further in-depth studies are necessary to clarify gene functions in the pathogenesis and immune evasion mechanisms of the infective larvae.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1218965","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T13:54:14Z","timestamp":1691157254000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of immune response against third-stage Gnathostoma spinigerum larvae by human 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