{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:17:20Z","timestamp":1789168640901,"version":"build-2803163510"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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:p>\n                    Helminths have evolved complex immunomodulatory mechanisms that enable chronic infection while minimizing host damage. This review summarizes recent advances in understanding nematode-derived molecules with therapeutic potential. The phosphorylcholine-modified glycoprotein ES-62 from\n                    <jats:italic>Acanthocheilonema viteae<\/jats:italic>\n                    exemplifies pathway-selective immune regulation and has inspired small-molecule analogues for inflammatory diseases.\n                    <jats:italic>Ancylostoma duodenale<\/jats:italic>\n                    secretes protease inhibitors, anticoagulants, and anti-inflammatory proteins that reveal targets for immune and hemostatic modulation.\n                    <jats:italic>Anisakis pegreffii<\/jats:italic>\n                    exerts context-dependent immune control via dendritic cell tolerization, macrophage polarization, and regulatory T-cell expansion. The cystatin Al-CPI from\n                    <jats:italic>Ascaris lumbricoides<\/jats:italic>\n                    reprograms dendritic cell metabolism, induces immune tolerance, and shows efficacy in colitis and allergy models.\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    secretes proteins that modulate antigen presentation, complement activation, and cytokine signaling. Together, these findings highlight helminth-derived compounds as blueprints for precision immunotherapies that restore immune homeostasis with minimal side effects.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1725730","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:20:50Z","timestamp":1776313250000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Nematodes immunomodulatory mechanisms and possible clinical application"],"prefix":"10.3389","volume":"17","author":[{"given":"Nikodem","family":"\u015awiderski","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Medical University of Silesia","place":["Katowice, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Gumienny","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical University of Silesia","place":["Katowice, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bielecka-Wajdman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical University of Silesia","place":["Katowice, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1462399408000720","article-title":"Therapeutic immunomodulators from nematode parasites","volume":"10","author":"Harnett","year":"2008","journal-title":"Expert Rev Mol Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7554\/elife.105393","article-title":"Coevolutionary interplay: Helminths-trained immunity and its impact on the rise of inflammatory diseases","volume":"14","author":"Carrera Silva","year":"2025","journal-title":"Elife"},{"key":"B3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.imlet.2004.04.008","article-title":"ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential","volume":"94","author":"Harnett","year":"2004","journal-title":"Immunol Lett"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2174\/1389203033380368","article-title":"Structural\/functional aspects of ES-62-A secreted immunomodulatory phosphorylcholine-containing filarial nematode glycoprotein","volume":"4","author":"Harnett","year":"2003"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.05.009","article-title":"An anticoagulant peptide from the hookworm, Ancylostoma duodenale that inhibits coagulation factors Xa and XIa","volume":"583","author":"Gan","year":"2009","journal-title":"FEBS Lett"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-010-2055-z","article-title":"Identification and characterization of a serine protease inhibitor with two trypsin inhibitor-like domains from the human hookworm Ancylostoma duodenale","volume":"108","author":"Jin","year":"2011","journal-title":"Parasitol Res"},{"key":"B7","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":"B8","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182021000214","article-title":"Helminth-derived cystatins: The immunomodulatory properties of an Ascaris lumbricoides cystatin","volume":"148","author":"Caraballo","year":"2021","journal-title":"Parasitology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2019.111233","article-title":"2 Brugia malayi galectin 2 is a tandem-repeat type galectin capable of binding mammalian polysaccharides","volume":"235","author":"Hertz","year":"2020","journal-title":"Mol Biochem Parasitol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-015-0515-z","article-title":"3 immuno-modulatory effect and therapeutic potential of brugia malayi cystatin in experimentally induced arthritis","volume":"31","author":"Yadav","year":"2016","journal-title":"Indian J Clin Biochem"},{"key":"B11","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jneuroim.2011.01.002","article-title":"The impact of parasite infections on the course of multiple sclerosis","volume":"233","author":"Correale","year":"2011","journal-title":"J Neuroimmunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21438","article-title":"Helminth infections associated with multiple sclerosis induce regulatory B cells","volume":"64","author":"Correale","year":"2008","journal-title":"Ann Neurol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009176","article-title":"GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection","volume":"16","author":"Ortiz Wilczy\u00f1ski","year":"2020","journal-title":"PLoS Pathog"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molbiopara.2014.03.003","article-title":"ES-62, a therapeutic anti-inflammatory agent evolved by the filarial nematode Acanthocheilonema viteae","volume":"194","author":"Pineda","year":"2014","journal-title":"Mol Biochem Parasitol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/srep37276","article-title":"The helminth product, ES-62 modulates dendritic cell responses by inducing the selective autophagolysosomal degradation of TLR-transducers, as exemplified by PKC\u03b4","volume":"6","author":"Eason","year":"2016","journal-title":"Sci Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26125576","article-title":"Chromosome-contiguous ancylostoma duodenale reference genome from a single archived specimen elucidates human hookworm biology and host\u2013parasite interactions \u2020","volume":"26","author":"Young","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12911","article-title":"Hookworm infections: Reappraising the evidence for a role of neutrophils in light of NETosis","volume":"44","author":"Doolan","year":"2022","journal-title":"Parasite Immunol"},{"key":"B18","volume-title":"Secretion of A proteolytic anticoagulant","author":"Hookworms","year":""},{"key":"B19","article-title":"Hyaluronidase from infective ancylostoma hookworm larvae and its possible function as a virulence factor in tissue invasion and in cutaneous larva migrans","volume-title":"Infection and immunity","author":"Hotez","year":"1992"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fpara.2023.1244604","article-title":"Immunomodulatory proteins from hookworms reduce cardiac inflammation and modulate regulatory responses in a mouse model of chronic Trypanosoma cruzi infection","volume":"2","author":"Jones","year":"2023","journal-title":"Front Parasitol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1595093","article-title":"Dual roles of Anisakis pegreffii proteins in macrophage immune dynamics","volume":"16","author":"Zeng","year":"2025","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1590\/0074-02760200560","article-title":"Expansion of t regulatory lymphocytes by murine bone marrow dendritic cells previously stimulated with anisakis simplex larval antigens","volume":"116","author":"Zamora","year":"2021","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B23","doi-asserted-by":"publisher","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":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1328401","article-title":"Cystatin from the helminth Ascaris lumbricoides upregulates mevalonate and cholesterol biosynthesis pathways and immunomodulatory genes in human monocyte-derived dendritic cells","volume":"15","author":"Acevedo","year":"2024","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096069","article-title":"Structural basis for the immunomodulatory function of cysteine protease inhibitor from human roundworm Ascaris lumbricoides","volume":"9","author":"Mei","year":"2014","journal-title":"PLoS One"},{"key":"B26","article-title":"Intestinal Mucosal Immunity: The interface of the host-xenobiont interactions","volume-title":"Isolation Of Non-Polar Metabolites In Excretory\/Secretory Products From Parasitic Helminths And Their Potential As Immunotherapy In Inflammatory Bowel Disease","author":"Siciliani","year":""},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02280","article-title":"Ascaris lumbricoides cystatin prevents development of allergic airway inflammation in a mouse model","volume":"10","author":"Coronado","year":"2019","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/biology12101340","article-title":"Comparison of Antibody Responses against Two Molecules from Ascaris lumbricoides: The Allergen Asc l 5 and the Immunomodulatory Protein Al-CPI","volume":"12","author":"Ahumada","year":"2023","journal-title":"Biol (Basel)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12425","article-title":"A recombinant cystatin from Ascaris lumbricoides attenuates inflammation of DSS-induced colitis","volume":"39","author":"Coronado","year":"2017","journal-title":"Parasite Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1436818","article-title":"Brugia malayi filarial helminth-derived extracellular vesicles suppress antigen presenting cell function and antigen-specific CD4+ T cell responses","volume":"15","author":"Sanku","year":"2024","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.micpath.2017.09.015","article-title":"4 Recombinant Brugia malayi pepsin inhibitor (rBm33) exploits host signaling events to regulate inflammatory responses associated with lymphatic filarial infections","volume":"112","author":"Sreenivas","year":"2017","journal-title":"Microb Pathog"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.parepi.2019.e00092","article-title":"5 Immunological evaluation of fusion protein of Brugia malayi abundant larval protein transcript-2 (BmALT-2) and Tuftsin in experimental mice model","volume":"4","author":"Paul","year":"2019","journal-title":"Parasite Epidemiol Control"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1017\/S0022149X1600064X","article-title":"6 Therapeutic potential of the immunomodulatory proteins Wuchereria bancrofti L2 and Brugia malayi abundant larval transcript 2 against streptozotocin-induced type 1 diabetes in mice","volume":"91","author":"Amdare","year":"2017","journal-title":"J Helminthol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00565","article-title":"7 Immunization with Brugia malayi Calreticulin Protein Generates Robust Antiparasitic Immunity and Offers Protection during Experimental Lymphatic Filariasis","volume":"7","author":"Yadav","year":"2021","journal-title":"ACS Infect Dis"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106413","article-title":"8 In silico and in vitro studies on the protein-protein interactions between Brugia malayi immunomodulatory protein calreticulin and human C1q","volume":"9","author":"Yadav","year":"2014","journal-title":"PLoS One"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00317-21","article-title":"10 localization and RNA interference-driven inhibition of a brugia malayi-encoded interleukin-5 receptor binding protein","volume":"90","author":"Mejia","year":"2022","journal-title":"Infect Immun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.22159\/ajpcr.2024v17i2.49210","article-title":"9 liposomal delivery of immunomodulatory antigen of B. Malayi: isolation, preparation, characterization, and immune responses assessment","volume":"17","author":"Jain","year":"2024","journal-title":"AJPCR"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00552","article-title":"10 Cathepsin L3 from fasciola hepatica induces NLRP3 inflammasome alternative activation in murine dendritic cells","volume":"10","author":"Celias","year":"2019","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00664","article-title":"09 Helminth infections: Recognition and modulation of the immune response by innate immune cells","volume":"9","author":"Motran","year":"2018","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1096\/fj.201500093R","article-title":"FJ The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages","volume":"31","author":"Alvarado","year":"2017","journal-title":"FASEB J"},{"key":"B41","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.pt.2016.05.004","article-title":"Eosinophils in helminth infection: defenders and dupes","volume":"32","author":"Huang","year":"2016","journal-title":"Trends Parasitol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.572865","article-title":"Immunomodulation and immune escape strategies of gastrointestinal helminths and schistosomes","volume":"11","author":"Wiedemann","year":"2020","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1725730\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:20:51Z","timestamp":1776313251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1725730\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2026.1725730"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1725730","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"article-number":"1725730"}}