{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T14:31:48Z","timestamp":1784817108383,"version":"3.55.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Anisakis pegreffii<\/jats:italic> is a zoonotic marine nematode whose life-cycle involves marine organisms\u2013small crustaceans, fish and squids as intermediate\/paratenic hosts, and marine mammals, mainly cetaceans\u2013as definitive ones. When its third-stage larvae (L3) are accidentally ingested by humans with the consumption of raw or undercooked parasitized fish and\/or squids, the parasite fails to complete its life cycle, leading to human anisakiasis. Despite increasing interest in understanding the molecular basis of pathogenic effects in human anisakiasis, the transcriptomic response of <jats:italic>A. pegreffii<\/jats:italic> L3 to interaction with human immune cells, remains poorly understood. Thus, in this study, the transcriptomic profile of <jats:italic>A. pegreffii<\/jats:italic> L3 larvae under <jats:italic>in vitro<\/jats:italic> exposure to human dendritic cells (DCs) was performed for the first time. A total of 3914 differentially expressed genes (DEGs) were identified in <jats:italic>A. pegreffii<\/jats:italic> L3 after exposure to immature DCs (iDCs), by RNA-seq, allowing to detect 1868 upregulated and 2046 downregulated transcripts. Upregulated genes were significantly enriched in pathways related to energy metabolism, oxidative stress response and structural maintenance, suggesting active metabolic and structural adaptation to immune-induced stress. Conversely, genes involved in cytoskeletal organization and intracellular trafficking were downregulated, potentially reflecting the parasite\u2019s developmental arrest in an unsuitable host such as humans. These findings provide novel insights into the molecular response pathways activated by this zoonotic parasite during the early stages of interaction with the human immune system.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1646537","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:28:39Z","timestamp":1757914119000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Transcriptomic profile of the zoonotic parasite Anisakis pegreffii upon in vitro exposure to human dendritic cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Marialetizia","family":"Palomba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelia","family":"Rughetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Castrignan\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Napoletano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Roca-Geron\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Pinna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Liberati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Canestrelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Mattiucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1128\/CMR.00012-07","article-title":"Anisakis simplex: from obscure infectious worm to inducer of immune hypersensitivity","volume":"21","author":"Audicana","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1186\/s13071-024-06471-7","article-title":"Anisakis extracellular vesicles elicit immunomodulatory and potentially tumorigenic outcomes on human intestinal organoids","volume":"17","author":"Bellini","year":"2025","journal-title":"Parasitol. Vectors."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12060777","article-title":"Basophil activation test in the diagnosis of Anisakis allergy: An observational study from an area of high seafood consumption in Italy","volume":"12","author":"Brusca","year":"2023","journal-title":"Pathogens"},{"key":"B4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nmeth.3176","article-title":"Fast and sensitive protein alignment using DIAMOND","volume":"12","author":"Buchfink","year":"2014","journal-title":"Nat. Methods"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5825","DOI":"10.1093\/molbev\/msab293","article-title":"eggNOG-mapper v2: Functional annotation, orthology assignments, and domain prediction at the metagenomic scale","volume":"38","author":"Cantalapiedra","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-S1-S6","article-title":"The MEPS server for identifying protein conformational epitopes","volume":"8","author":"Castrignan\u00f2","year":"2007","journal-title":"BMC Bioinform."},{"key":"B7","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1186\/s12859-020-03565-8","article-title":"ELIXIR-IT HPC @ CINECA: High performance computing resources for the bioinformatics community","volume":"21","author":"Castrignan\u00f2","year":"2020","journal-title":"BMC Bioinform."},{"key":"B8","doi-asserted-by":"publisher","first-page":"9667","DOI":"10.1038\/s41598-022-13594-3","article-title":"A miRNAs catalogue from third-stage larvae and extracellular vesicles of Anisakis pegreffii provides new clues for host-parasite interplay","volume":"12","author":"Cavallero","year":"2022","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.fishres.2017.07.010","article-title":"The Mediterranean European hake, Merluccius merluccius: Detecting drivers influencing the Anisakis spp. larvae distribution","volume":"202","author":"Cipriani","year":"2018","journal-title":"Fish. Res."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-024-02091-w","article-title":"Adaptive evolution of stress response genes in parasites aligns with host niche diversity","volume":"23","author":"Cruz-Laufer","year":"2025","journal-title":"BMC Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.vetpar.2018.06.015","article-title":"The somatic proteins of Toxocara canis larvae and excretory-secretory products revealed by proteomics","volume":"259","author":"da Silva","year":"2018","journal-title":"Vet. Parasitol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02481","article-title":"Tumor-derived microvesicles enhance cross-processing ability of clinical grade dendritic cells","volume":"9","author":"Dionisi","year":"2018","journal-title":"Front. Immunol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2024.9090","article-title":"Re-evaluation of certain aspects of the EFSA Scientific Opinion of April 2010 on risk assessment of parasites in fishery products, based on new scientific data","author":"Koutsoumanis","year":"2024","journal-title":"EFSA"},{"key":"B14","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1186\/s12859-020-03562-x","article-title":"HPC-REDItools: A novel HPC-aware tool for improved large-scale RNA-editing analysis","volume":"21","author":"Flati","year":"2020","journal-title":"BMC Bioinform."},{"key":"B15","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1083\/jcb.114.3.465","article-title":"Muscle cell attachment in Caenorhabditis elegans","volume":"14","author":"Francis","year":"1991","journal-title":"J. Cell. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1051\/parasite\/2018034","article-title":"Human anisakiasis in Italy: a retrospective epidemiological study over two decades","volume":"25","author":"Guardone","year":"2018","journal-title":"Parasite"},{"key":"B17","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/381571a0","article-title":"Molecular chaperones in cellular protein folding","volume":"381","author":"Hartl","year":"1996","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1083\/jcb.146.3.659","article-title":"Myotactin, a novel hypodermal protein involved in muscle-cell adhesion in Caenorhabditis elegans","volume":"146","author":"Hresko","year":"1999","journal-title":"J. Cell. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1016\/j.ijbiomac.2021.10.200","article-title":"Filarial thioredoxin reductase exerts anti-inflammatory effects upon lipopolysaccharide induced inflammation in macrophages","volume":"193","author":"Joardar","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/bies.950160307","article-title":"The cuticle of the nematode Caenorhabditis elegans: a complex collagen structure","volume":"16","author":"Johnstone","year":"1994","journal-title":"Bioessays"},{"key":"B21","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/s0168-9525(99)01857-0","article-title":"Cuticle collagen genes expression in Caenorhabditis elegans","volume":"16","author":"Johnstone","year":"2000","journal-title":"Trends Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3857","DOI":"10.1002\/j.1460-2075.1992.tb05478.x","article-title":"Molecular analysis of mutations in the Caenorhabditis elegans collagen gene dpy-7","volume":"1","author":"Johnstone","year":"1992","journal-title":"EMBO J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.molbiopara.2018.10.002","article-title":"Comparative transcriptome analyses of the third and fourth stage larvae of Anisakis simplex (Nematoda: Anisakidae)","volume":"226","author":"Kim","year":"2018","journal-title":"Mol. Biochem. Parasitol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2013 \u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"methods"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/icb.2015.114","article-title":"A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection","volume":"94","author":"Lundie","year":"2016","journal-title":"Immunol. Cell. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.jaci.2016.07.007","article-title":"Regulation of the host immune system by helminth parasites","volume":"138","author":"Maizels","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/bs.apar.2017.12.001","article-title":"Molecular epidemiology of Anisakis and Anisakiasis: an ecological and evolutionary road map","volume":"99","author":"Mattiucci","year":"2018","journal-title":"Adv. Parasitol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/pim.12440","article-title":"IgE sensitization to Anisakis pegreffii in Italy: Comparison of two methods for the diagnosis of allergic anisakiasis","volume":"39","author":"Mattiucci","year":"2017","journal-title":"Parasite Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"496","DOI":"10.3201\/eid1903.121017","article-title":"Anisakiasis and gastroallergic reactions associated with Anisakis pegreffii infection, Italy","volume":"19","author":"Mattiucci","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1017\/S0031182025000228","article-title":"Hybridization and introgression of mitochondrial genome between the two species Anisakis pegreffii and A. simplex (s. s.) using a wide genotyping approach: evolutionary and ecological implications","volume":"152","author":"Mattiucci","year":"2025","journal-title":"Parasitology"},{"key":"B32","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/B978-0-12-818731-9.00075-6","volume-title":"Encyclopedia of infection and immunity","author":"Mattiucci","year":"2022"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181277","article-title":"Immunomodulatory effects of excretory\/secretory compounds from Contracaecum osculatum larvae in a zebrafish inflammation model","volume":"12","author":"Mehrdana","year":"2017","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12527","article-title":"Anisakis pegreffii impacts differentiation and function of human dendritic cells","volume":"40","author":"Napoletano","year":"2018","journal-title":"Parasite Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1097\/CJI.0b013e318046f396","article-title":"A comparative analysis of serum and serum-free media for generation of clinical grade DCs","volume":"30","author":"Napoletano","year":"2007","journal-title":"J. Immunother."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1042\/BST20180480","article-title":"Calcium and Ca 2+\/Calmodulin-dependent kinase II as targets for helminth parasite control","volume":"46","author":"Nawaratna","year":"2018","journal-title":"Biochem. Soc Trans."},{"key":"B37","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/pim.12349","article-title":"Anisakis\u2013immunology of a foodborne parasitosis","volume":"38","author":"Nieuwenhuizen","year":"2016","journal-title":"Parasite Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.ijpara.2013.08.001","article-title":"Anisakis-a food-borne parasite that triggers allergic host defences","volume":"43","author":"Nieuwenhuizen","year":"2013","journal-title":"Int. J. Parasitol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1895\/wormbook.1.138.1","article-title":"The cuticle","author":"Page","year":"2007","journal-title":"WormBook"},{"key":"B40","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.ijpddr.2014.05.003","article-title":"Enzymology of the nematode cuticle: a potential drug target","volume":"4","author":"Page","year":"2014","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"B41","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s13104-022-06099-9","article-title":"De novo transcriptome assembly and annotation of the third stage larvae of the zoonotic parasite Anisakis pegreffii","volume":"15","author":"Palomba","year":"2022","journal-title":"BMC Res. Notes"},{"key":"B42","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1051\/parasite\/2019055","article-title":"Gene expression profiles of antigenic proteins of third stage larvae of the zoonotic nematode Anisakis pegreffii in response to temperature conditions","volume":"26","author":"Palomba","year":"2019","journal-title":"Parasite"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1079991","article-title":"Proteomic characterization of extracellular vesicles released by third stage larvae of the zoonotic parasite Anisakis pegreffii (Nematoda: Anisakidae)","volume":"13","author":"Palomba","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1051\/parasite\/2020033","article-title":"A novel nuclear marker and development of an ARMS-PCR assay targeting the metallopeptidase 10 (nas 10) locus to identify the species of the Anisakis simplex (s. l.) complex (Nematoda, Anisakidae)","volume":"27","author":"Palomba","year":"2020","journal-title":"Parasite"},{"key":"B45","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.995432","article-title":"Communication is key: Innate immune cells regulate host protection to helminths","volume":"13","author":"Peng","year":"2022","journal-title":"Front. Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S0031182025100620","article-title":"Organoids in parasitology: a game-changer for studying host-nematode interactions","author":"Perez","year":"2025","journal-title":"Parasitology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1007\/s12192-015-0607-y","article-title":"The role of small heat shock proteins in parasites","volume":"20","author":"P\u00e9rez-Morales","year":"2015","journal-title":"Cell. Stress Chaperones"},{"key":"B49","first-page":"78","article-title":"IGUANER - differential gene expression and fUnctionAlaNalyzER","volume-title":"Lecture notes in computer science","author":"Pinna","year":"2024"},{"key":"B50","volume-title":"Immunol. Today","author":"Polla","year":"1991"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iya047","article-title":"Specific collagens maintain the cuticle permeability barrier in Caenorhabditis elegans","volume":"217","author":"Sandhu","year":"2021","journal-title":"Genetics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07391102.2023.2283876","article-title":"In silico exploration and in vitro validation of the filarial thioredoxin reductase inhibitory activity of Scytonemin and its derivatives","volume":"21","author":"Sen","year":"2023","journal-title":"J. Biomol. Struct. Dyn"},{"key":"B53","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1645\/GE-610R.1","article-title":"Radioresistance of Anisakis simplex third-stage larvae and the possible role of superoxide dismutase","volume":"92","author":"Seo","year":"2006","journal-title":"J. Parasitol."},{"key":"B54","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S0952-7915(03)00072-4","article-title":"Shaping the immune response to parasites: role of dendritic cells","volume":"15","author":"Sher","year":"2003","journal-title":"Curr. Opin. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"4336","DOI":"10.3390\/ijms23084336","article-title":"Tandem mass tagging (TMT) reveals tissue-specific proteome of L4 larvae of Anisakis simplex ss: Enzymes of energy and\/or carbohydrate metabolism as potential drug targets in anisakiasis","volume":"23","author":"Stryi\u0144ski","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2024.108751","article-title":"The response of Anisakis simplex (s. s.) to anthelmintics - Specific changes in xenobiotic metabolic processes","volume":"261","author":"Stryi\u0144ski","year":"2024","journal-title":"Exp. Parasitol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.1016\/j.ygeno.2021.06.032","article-title":"Molecular and evolutionary basis for survival, its failure, and virulence factors of the zoonotic nematode Anisakis pegreffii","volume":"113","author":"Trumbi\u0107","year":"2021","journal-title":"Genomics"},{"key":"B58","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1645\/GE-3504.1(2006","article-title":"Genetic relationships among Anisakis species (Nematoda: Anisakidae) inferred from mitochondrial cox2 sequences, and comparison with allozyme data","volume":"92","author":"Valentini","year":"2006","journal-title":"J. Parasitol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1051\/parasite\/2025018","article-title":"Effects of Trichinella spiralis excretory-secretory antigens on expression of indoleamine 2, 3-dioxygenase on dendritic cells in vitro","volume":"32","author":"Yu","year":"2025","journal-title":"Parasite"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108120","article-title":"Anisakis simplex: Immunomodulatory effects of larval antigens on the activation of Toll like Receptors. International","volume":"100","author":"Zamora","year":"2021","journal-title":"Immunopharmacol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"e12616","DOI":"10.1111\/pim.12616","article-title":"Induction of tolerogenic properties by Anisakis larval antigens on murine dendritic cells","volume":"41","author":"Zamora","year":"2019","journal-title":"Parasite Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1646537\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:28:42Z","timestamp":1757914122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1646537\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":61,"alternative-id":["10.3389\/fcimb.2025.1646537"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1646537","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]},"article-number":"1646537"}}