{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:05:01Z","timestamp":1790269501044,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012547","name":"Guangxi Natural Science Foundation","doi-asserted-by":"publisher","award":["2026GXNSFAA00640914"],"award-info":[{"award-number":["2026GXNSFAA00640914"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Project of Guangxi Graduate Education","award":["YCSE2023036"],"award-info":[{"award-number":["YCSE2023036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Fasciolosis, a disease induced by liver fluke infection, poses a major threat to the livestock industry. The emergence of drug resistance and the lack of commercial vaccines necessitate the development of novel control strategies. Studies on helminth immunoregulatory molecules have become a key research focus. Bone morphogenetic proteins (BMPs), ligand members of the TGF-\u03b2 superfamily, have been identified in Fasciola gigantica and designated FgBMPs, and are hypothesized to regulate host immune responses. To explore the effects of FgBMP on hosts, the mechanistic actions of FgBMP-1 on buffalo peripheral blood mononuclear cells (PBMCs) were investigated to preliminarily elucidate host\u2013parasite interactions. Molecular docking predicted strong binding between FgBMP-1 and buffalo BMP receptors. Immunostaining using specific monoclonal antibodies revealed the tissue distribution of FgBMP-1, confirming its expression in adult worms, juvenile worms, and excretory\u2013secretory products of F. gigantica (FgESP). Recombinant FgBMP-1 (rFgBMP-1) bound to buffalo PBMCs and significantly suppressed cell proliferation, migration, and phagocytosis while enhancing nitric oxide production. Transcriptional analysis showed that rFgBMP-1 downregulated IFN-\u03b3 and IL-10 transcription, whereas it upregulated IL-4 and TGF-\u03b2 transcription. Transcriptome analysis revealed that rFgBMP-1 may activate the classical TGF-\u03b2 and MAPK pathways independently or synergistically. Additionally, rFgBMP-1 may modulate host immune responses via crosstalk with the Th17 differentiation and Toll-like receptor signaling pathways. Therefore, FgBMP-1 may mediate immunosuppression in buffalo PBMCs via activation of the TGF-\u03b2 pathway, thereby refining the theoretical understanding of parasite immune evasion.<\/jats:p>","DOI":"10.3390\/ijms27198552","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:29:53Z","timestamp":1790267393000},"page":"8552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fasciolagigantica Recombinant Bone Morphogenetic Protein (FgBMP) Modulates Various Functions of Buffalo Peripheral Blood Mononuclear Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Xinping","family":"Kong","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"},{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"He","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-0286","authenticated-orcid":false,"given":"Wenda","family":"Di","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1365-3024.2010.01223.x","article-title":"Improving Animal and Human Health through Understanding Liver Fluke Immunology","volume":"32","author":"Piedrafita","year":"2010","journal-title":"Parasite Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Torgerson, P.R., Devleesschauwer, B., Praet, N., Speybroeck, N., Willingham, A.L., Kasuga, F., Rokni, M.B., Zhou, X.-N., F\u00e8vre, E.M., and Sripa, B. (2015). World Health Organization Estimates of the Global and Regional Disease Burden of 11 Foodborne Parasitic Diseases, 2010: A Data Synthesis. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001920"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ijpddr.2019.11.003","article-title":"Drug Resistance in Liver Flukes","volume":"12","author":"Fairweather","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1053\/rvsc.2000.0425","article-title":"Cathepsin L Proteinases as Vaccines against Infection with Fasciola hepatica (Liver Fluke) in Ruminants","volume":"70","author":"Mulcahy","year":"2001","journal-title":"Res. Vet. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.exppara.2013.06.010","article-title":"Vaccine Potential of Recombinant Cathepsin B against Fasciola gigantica","volume":"135","author":"Chantree","year":"2013","journal-title":"Exp. Parasitol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102353","DOI":"10.1016\/j.parint.2021.102353","article-title":"The Combined Recombinant Cathepsin L1H and Cathepsin B3 Vaccine against Fasciola gigantica Infection","volume":"83","author":"Kueakhai","year":"2021","journal-title":"Parasitol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molbiopara.2009.04.008","article-title":"Helminth Immunoregulation: The Role of Parasite Secreted Proteins in Modulating Host Immunity","volume":"167","author":"Hewitson","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"a022061","DOI":"10.1101\/cshperspect.a022061","article-title":"TGF-\u03b2 Signaling from Receptors to Smads","volume":"8","author":"Hata","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.cellsig.2018.09.002","article-title":"TGF-\u03b2 Receptors: In and beyond TGF-\u03b2 Signaling","volume":"52","author":"Cao","year":"2018","journal-title":"Cell Signal"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tzavlaki, K., and Moustakas, A. (2020). TGF-\u03b2 Signaling. Biomolecules, 10.","DOI":"10.3390\/biom10030487"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.ijpara.2010.02.013","article-title":"Growth Factors and Chemotactic Factors from Parasitic Helminths: Molecular Evidence for Roles in Host-Parasite Interactions versus Parasite Development","volume":"40","author":"Freitas","year":"2010","journal-title":"Int. J. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sulaiman, A.A., Zolnierczyk, K., Japa, O., Owen, J.P., Maddison, B.C., Emes, R.D., Hodgkinson, J.E., Gough, K.C., and Flynn, R.J. (2016). A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005991"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nono, J.K., Lutz, M.B., and Brehm, K. (2020). Expansion of Host Regulatory T Cells by Secreted Products of the Tapeworm Echinococcus multilocularis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00798"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e442","DOI":"10.1111\/j.1365-2567.2008.02998.x","article-title":"Effect of Bone Morphogenetic Protein-6 on Macrophages","volume":"128","author":"Hong","year":"2009","journal-title":"Immunology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"a021899","DOI":"10.1101\/cshperspect.a021899","article-title":"Bone Morphogenetic Proteins","volume":"8","author":"Katagiri","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7388","DOI":"10.1158\/1078-0432.CCR-17-1004","article-title":"BMP4 Induces M2 Macrophage Polarization and Favors Tumor Progression in Bladder Cancer","volume":"23","author":"Rubio","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.1111\/jcmm.13814","article-title":"BMP-2 Induces Human Mononuclear Cell Chemotaxis and Adhesion and Modulates Monocyte-to-Macrophage Differentiation","volume":"22","author":"Pardali","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.meegid.2017.03.007","article-title":"De Novo Transcriptome Sequencing and Analysis of the Juvenile and Adult Stages of Fasciola gigantica","volume":"51","author":"Zhang","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00436-023-08064-2","article-title":"Reconstruction of the TGF-\u03b2 Signaling Pathway of Fasciola gigantica","volume":"123","author":"Wu","year":"2023","journal-title":"Parasitol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106676","DOI":"10.1016\/j.actatropica.2022.106676","article-title":"Schistosome Secretomes","volume":"236","author":"Skelly","year":"2022","journal-title":"Acta Trop."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1074\/mcp.M115.053934","article-title":"The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis","volume":"14","author":"Cwiklinski","year":"2015","journal-title":"Mol. Cell Proteom."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bennett, A.P.S., de la Torre-Escudero, E., Dermott, S.S.E., Threadgold, L.T., Hanna, R.E.B., and Robinson, M.W. (2022). Fasciola hepatica Gastrodermal Cells Selectively Release Extracellular Vesicles via a Novel Atypical Secretory Mechanism. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105525"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ganesan, N., Ronsmans, S., and Hoet, P. (2023). Methods to Assess Proliferation of Stimulated Human Lymphocytes in Vitro: A Narrative Review. Cells, 12.","DOI":"10.3390\/cells12030386"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.imbio.2015.02.001","article-title":"Fasciola hepatica Excretory-Secretory Products Induce CD4+T Cell Anergy via Selective up-Regulation of PD-L2 Expression on Macrophages in a Dectin-1 Dependent Way","volume":"220","author":"Guasconi","year":"2015","journal-title":"Immunobiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/eji.201545905","article-title":"Fasciola Hepatica Tegumental Antigens Induce Anergic-like T Cells via Dendritic Cells in a Mannose Receptor-Dependent Manner","volume":"46","author":"Aldridge","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"46748","DOI":"10.1038\/srep46748","article-title":"Fasciola hepatica Glycoconjugates Immuneregulate Dendritic Cells through the Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Non-Integrin Inducing T Cell Anergy","volume":"7","author":"Kalay","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.4049\/jimmunol.146.8.2719","article-title":"Molecular Basis of \u201cSuppressor\u201d Macrophages. Arginine Metabolism via the Nitric Oxide Synthetase Pathway","volume":"146","author":"Mills","year":"1991","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1017\/S0031182017000841","article-title":"Helminth-Induced Apoptosis: A Silent Strategy for Immunosuppression","volume":"144","author":"Zakeri","year":"2017","journal-title":"Parasitology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.vetimm.2007.03.007","article-title":"Excretory-Secretory Products from Fasciola hepatica Induce Eosinophil Apoptosis by a Caspase-Dependent Mechanism","volume":"117","author":"Serradell","year":"2007","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.vetimm.2012.06.022","article-title":"Fasciola hepatica Products Induce Apoptosis of Peritoneal Macrophages","volume":"148","author":"Guasconi","year":"2012","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1128\/IAI.69.1.271-280.2001","article-title":"Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL(+) T and B Cells during Murine Schistosoma Mansoni Infection","volume":"69","author":"Lundy","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1128\/IAI.70.2.812-819.2002","article-title":"Fas Ligand-Expressing B-1a Lymphocytes Mediate CD4(+)-T-Cell Apoptosis during Schistosomal Infection: Induction by Interleukin 4 (IL-4) and IL-10","volume":"70","author":"Lundy","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1006\/meth.1996.0072","article-title":"Nitrogen Oxide in Host Defense against Parasites","volume":"10","author":"Oswald","year":"1996","journal-title":"Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.immunol.15.1.323","article-title":"Nitric Oxide and Macrophage Function","volume":"15","author":"MacMicking","year":"1997","journal-title":"Annu Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Xue, Q., Yan, Y., Zhang, R., and Xiong, H. (2018). Regulation of iNOS on Immune Cells and Its Role in Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123805"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10214","DOI":"10.1073\/pnas.1708578114","article-title":"Nitric Oxide Blocks the Development of the Human Parasite Schistosoma japonicum","volume":"114","author":"Shen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1590\/S0074-02762005000900012","article-title":"Nitric Oxide and the Resolution of Inflammation: Implications for Atherosclerosis","volume":"100","author":"Shaw","year":"2005","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Shen, J., Yu, S.-F., Peng, M., Lai, D.-H., Hide, G., Wu, Z.-D., and Lun, Z.-R. (2022). iNOS Is Essential to Maintain a Protective Th1\/TH2 Response and the Production of Cytokines\/Chemokines against Schistosoma japonicum Infection in Rats. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010403"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhao, Z.-J., Zhu, X.-Q., Ren, Q.-S., Nie, F.-F., Gao, J.-M., Gao, X.-J., Yang, T.-B., Zhou, W.-L., and Shen, J.-L. (2012). Differences in iNOS and Arginase Expression and Activity in the Macrophages of Rats Are Responsible for the Resistance against T. gondii Infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035834"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1083\/jcb.201004096","article-title":"Clearance of Apoptotic Cells: Implications in Health and Disease","volume":"189","author":"Elliott","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/cdd.2015.172","article-title":"The Clearance of Dying Cells: Table for Two","volume":"23","author":"Green","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.immuni.2016.02.005","article-title":"Boosting Apoptotic Cell Clearance by Colonic Epithelial Cells Attenuates Inflammation in Vivo","volume":"44","author":"Lee","year":"2016","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev-immunol-042617-053010","article-title":"Apoptosis and Clearance of Apoptotic Cells","volume":"36","author":"Nagata","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_44","first-page":"F1000 Faculty Rev-1685","article-title":"Helminth Parasites and Immune Regulation","volume":"7","author":"Nutman","year":"2018","journal-title":"F1000Res"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.pt.2023.04.002","article-title":"Regulatory T Cells in Parasite Infections: Susceptibility, Specificity and Specialisation","volume":"39","author":"McManus","year":"2023","journal-title":"Trends Parasitol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1002\/eji.1830270920","article-title":"A Filarial Cysteine Protease Inhibitor Down-Regulates T Cell Proliferation and Enhances Interleukin-10 Production","volume":"27","author":"Hartmann","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zheng, M., Jiang, X., Kong, X., Guo, Y., Zhang, W., and Di, W. (2022). Proteomic Analysis of Fasciola gigantica Excretory and Secretory Products (FgESPs) Co-Immunoprecipitated Using a Time Course of Infected Buffalo Sera. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1089394"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1186\/s13071-024-06570-5","article-title":"Immune Modulation of Buffalo Peripheral Blood Mononuclear Cells by Two Asparaginyl Endopeptidases from Fasciola gigantica","volume":"17","author":"Wu","year":"2024","journal-title":"Parasit. Vectors"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8552\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:30:53Z","timestamp":1790267453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":48,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198552"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198552","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}