{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:48:06Z","timestamp":1791337686567,"version":"4.3.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"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. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cystic echinococcosis, caused by the larval stage of <jats:italic>Echinococcus granulosus<\/jats:italic>, remains a global health challenge. Mesenchymal stem cells (MSCs) are renowned for their regenerative and immunomodulatory properties. Given the parasite\u2019s mode of establishment, we postulate that MSCs likely play a pivotal role in the interaction between the parasite and the host. This study aims to explore the response of MSCs to antigens derived from <jats:italic>Echinococcus granulosus<\/jats:italic>, the etiological agent of hydatid disease, with the hypothesis that exposure to these antigens may alter MSC function and impact the host\u2019s immune response to the parasite.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MSCs were isolated from mouse bone marrow and co-cultured with ESPs, HCF, or pLL antigens. We conducted high-throughput sequencing to examine changes in the MSCs\u2019 mRNA expression profile. Additionally, cell cycle, migration, and secretory functions were assessed using various assays, including CCK8, flow cytometry, real-time PCR, Western blot, and ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis revealed that hydatid antigens significantly modulate the mRNA expression of genes related to cytokine and chemokine activity, impacting MSC proliferation, migration, and cytokine secretion. Specifically, there was a downregulation of chemokines (MCP-1, CXCL1) and pro-inflammatory cytokines (IL-6, NOS2\/NO), alongside an upregulation of anti-inflammatory mediators (COX2\/PGE2). Furthermore, all antigens reduced MSC migration, and significant alterations in cellular metabolism-related pathways were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hydatid disease antigens induce a distinct immunomodulatory response in MSCs, characterized by a shift towards an anti-inflammatory phenotype and reduced cell migration. These changes may contribute to the parasite\u2019s ability to evade host defenses and persist within the host, highlighting the complex interplay between MSCs and hydatid disease antigens. This study provides valuable insights into the pathophysiology of hydatid disease and may inform the development of novel therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1381401","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T04:59:40Z","timestamp":1712638780000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunomodulatory effects of hydatid antigens on mesenchymal stem cells: gene expression alterations and functional consequences"],"prefix":"10.3389","volume":"15","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wubulikasimu","family":"Mijiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifei","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyu","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengru","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.ydbio.2018.03.002","article-title":"Extracellular matrix dynamics during mesenchymal stem cells differentiation","volume":"437","author":"Assis-Ribas","year":"2018","journal-title":"Dev. 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Immun."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"748404","DOI":"10.3389\/fcimb.2021.748404","article-title":"The nf-\u03bab pathway: modulation by entamoeba histolytica and other protozoan parasites","volume":"11","author":"Chadha","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e252163","DOI":"10.1371\/journal.pone.0252163","article-title":"Interleukin-1\u03b2-induced matrix metalloproteinase-3 via erk1\/2 pathway to promote mesenchymal stem cell migration","volume":"16","author":"Chang","year":"2021","journal-title":"PLoS One"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"702125","DOI":"10.3389\/fcimb.2021.702125","article-title":"Revisiting the mechanisms of immune evasion employed by human parasites","volume":"11","author":"Chulanetra","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4161\/org.7.2.16150","article-title":"Multilineage stem cells in the adult","volume":"7","author":"Crisan","year":"2014","journal-title":"Organogenesis"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"591065","DOI":"10.3389\/fimmu.2020.591065","article-title":"Immunomodulatory and regenerative effects of mesenchymal stem cells and extracellular vesicles: therapeutic outlook for inflammatory and degenerative diseases","volume":"11","author":"Dabrowska","year":"2021","journal-title":"Front. Immunol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/2989076","article-title":"Effects of oxidative stress on mesenchymal stem cell biology","volume":"2016","author":"Denu","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.pt.2010.12.012","article-title":"Understanding the laminated layer of larval echinococcus i: structure","volume":"27","author":"D\u00edaz","year":"2011","journal-title":"Trends Parasitol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"BSR20180916","DOI":"10.1042\/BSR20180916","article-title":"The state of art of neutrophil extracellular traps in protozoan and helminthic infections","volume":"39","author":"D\u00edaz-God\u00ednez","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.1002\/eji.201141499","article-title":"Mesenchymal stem cell inhibition of t-helper 17 cell- differentiation is triggered by cell-cell contact and mediated by prostaglandin e2 via the ep4 receptor","volume":"41","author":"Duffy","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/icb.2012.56","article-title":"Mechanisms of mesenchymal stromal cell immunomodulation","volume":"91","author":"English","year":"2013","journal-title":"Immunol. Cell Biol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.3390\/ijms22073576","article-title":"Mesenchymal stem cells as a cornerstone in a galaxy of intercellular signals: basis for a new era of medicine","volume":"22","author":"Fern\u00e1ndez-Francos","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref16","first-page":"1","article-title":"Immunology of Alveolar and Cystic Echinococcosis (AE and CE)","volume-title":"Adv. Parasitol","author":"Gottstein","year":"2017"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1051\/parasite\/2014063","article-title":"Echinococcus metacestode: in search of viability markers","volume":"21","author":"Gottstein","year":"2014","journal-title":"Parasite"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1186\/s12967-019-02167-0","article-title":"The immunoregulation of mesenchymal stem cells plays a critical role in improving the prognosis of liver transplantation","volume":"17","author":"Hu","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1128\/mr.59.4.533-547.1995","article-title":"Role of nitric oxide in parasitic infections","volume":"59","author":"James","year":"1995","journal-title":"Microbiol. Rev."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/j.1365-2567.2006.02375.x","article-title":"Modulation of dendritic cell differentiation and cytokine secretion by the hydatid cyst fluid of Echinococcus granulosus","volume":"118","author":"Kanan","year":"2006","journal-title":"Immunology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1007\/s11686-022-00620-7","article-title":"Efficacy of mesenchymal stem cells therapy in parasitic infections: are anti-parasitic drugs combined with MSCs more effective?","volume":"67","author":"Kian","year":"2022","journal-title":"Acta Parasitol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"287","DOI":"10.3390\/biom12020287","article-title":"Ibuprofen in therapeutic concentrations affects the secretion of human bone marrow mesenchymal stromal cells, but not their proliferative and migratory capacity","volume":"12","author":"Kulesza","year":"2022","journal-title":"Biomolecules"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"856","DOI":"10.2533\/chimia.2016.856","article-title":"Chemokines: chemistry, biochemistry and biological function","volume":"70","author":"Legler","year":"2016","journal-title":"Chimia"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1017\/S0031182021000548","article-title":"Echinococcus granulosus cyst fluid suppresses inflammatory responses by inhibiting traf6 signalling in macrophages","volume":"148","author":"Lin","year":"2021","journal-title":"Parasitology"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"87","DOI":"10.47176\/mjiri.37.87","article-title":"Evaluation of hydatid cyst antigen for serological diagnosis","volume":"37","author":"Maleki","year":"2023","journal-title":"Med. J. Islam Repub. Iran"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e12533","DOI":"10.1111\/pim.12533","article-title":"Echinococcus granulosus cyst fluid enhances epithelial-mesenchymal transition","volume":"40","author":"Mohammed","year":"2018","journal-title":"Parasite Immunol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/9919361","article-title":"An in vitro and in vivo comparison of osteogenic differentiation of human mesenchymal stromal\/stem cells","volume":"2021","author":"Mollentze","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1080\/14787210.2017.1401466","article-title":"Management of osseous cystic echinococcosis","volume":"15","author":"Monge-Maillo","year":"2017","journal-title":"Expert Rev. Anti-Infect. 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Vectors"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e3392","DOI":"10.1371\/journal.pntd.0003392","article-title":"Transcriptome profiles of the protoscoleces of Echinococcus granulosus reveal that excretory-secretory products are essential to metabolic adaptation","volume":"8","author":"Pan","year":"2014","journal-title":"Plos Neglect. Trop. Dis."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/s13287-018-1039-2","article-title":"Preconditioning of bone marrow-derived mesenchymal stem cells highly strengthens their potential to promote il-6-dependent m2b polarization","volume":"9","author":"Philipp","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5607","DOI":"10.1007\/s11033-021-06360-7","article-title":"The secretome of mesenchymal stem cells and oxidative stress: challenges and opportunities in cell-free regenerative medicine","volume":"48","author":"Rahimi","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref35","first-page":"409","article-title":"Oxysterols and mesenchymal stem cell biology","volume-title":"Vitam. Horm","author":"Reichert","year":"2021"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13071-016-1350-7","article-title":"Echinococcus granulosus antigen b binds to monocytes and macrophages modulating cell response to inflammation","volume":"9","author":"Silva-\u00c1lvarez","year":"2016","journal-title":"Parasites Vectors"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12950-015-0063-6","article-title":"Crude extract of hydatid laminated layer from Echinococcus granulosus cyst attenuates mucosal intestinal damage and inflammatory responses in dextran sulfate sodium induced colitis in mice","volume":"12","author":"Soufli","year":"2015","journal-title":"J. Inflamm."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1046\/j.1365-3024.2001.00385.x","article-title":"In-vitro susceptibility of hydatid cysts of Echinococcus granulosus to nitric oxide and the effect of the laminated layer on nitric oxide production","volume":"23","author":"Steers","year":"2001","journal-title":"Parasite Immunol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1093\/jac\/dkt429","article-title":"Treatment challenges associated with bone echinococcosis","volume":"69","author":"Steinmetz","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.3390\/ijms24021277","article-title":"Pretreated mesenchymal stem cells and their secretome: enhanced immunotherapeutic strategies","volume":"24","author":"Su","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"a16295","DOI":"10.1101\/cshperspect.a016295","article-title":"Il-6 in inflammation, immunity, and disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"105306","DOI":"10.1016\/j.actatropica.2019.105306","article-title":"Potential role of nf-\u03bab pathway in the immuno-inflammatory responses during human cystic echinococcosis","volume":"203","author":"Tilioua","year":"2020","journal-title":"Acta Trop."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1186\/s13071-019-3786-z","article-title":"Thioredoxin peroxidase secreted by echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K\/AKT\/mTOR pathway","volume":"12","author":"Wang","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"13310","DOI":"10.3390\/ijms222413310","article-title":"The framework for human host immune responses to four types of parasitic infections and relevant key jak\/stat signaling","volume":"22","author":"Wen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e21851","DOI":"10.1096\/fj.202002808RR","article-title":"CCL2 is a critical mechano-responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells","volume":"35","author":"Yao","year":"2021","journal-title":"FASEB J."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e162436","DOI":"10.1172\/jci.insight.162436","article-title":"The m6a methyltransferase mettl16 negatively regulates mcp1 expression in mesenchymal stem cells during monocyte recruitment","volume":"8","author":"Zhang","year":"2023","journal-title":"JCI Insight"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"688128","DOI":"10.3389\/fcell.2021.688128","article-title":"Toxocara canis infection alters lncRNA and mRNA expression profiles of dog bone marrow","volume":"9","author":"Zheng","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12929-021-00725-7","article-title":"Mesenchymal stem\/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications","volume":"28","author":"Zhuang","year":"2021","journal-title":"J. Biomed. 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