{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:07:18Z","timestamp":1760058438593,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"key project from the Sichuan Province of China","award":["2017HH0023","2020YFH0020","2021YFYZ0030","2015NY-02-0028-NC","XYZS2021-02"],"award-info":[{"award-number":["2017HH0023","2020YFH0020","2021YFYZ0030","2015NY-02-0028-NC","XYZS2021-02"]}]},{"name":"key project of Chengdu","award":["2017HH0023","2020YFH0020","2021YFYZ0030","2015NY-02-0028-NC","XYZS2021-02"],"award-info":[{"award-number":["2017HH0023","2020YFH0020","2021YFYZ0030","2015NY-02-0028-NC","XYZS2021-02"]}]},{"name":"Open Project of New Drug Pre-production Key Laboratory of Sichuan Province","award":["2017HH0023","2020YFH0020","2021YFYZ0030","2015NY-02-0028-NC","XYZS2021-02"],"award-info":[{"award-number":["2017HH0023","2020YFH0020","2021YFYZ0030","2015NY-02-0028-NC","XYZS2021-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>China\u2019s livestock industry grapples with challenges posed by infectious diseases and the misuse of antibiotics, resulting in a heightened risk of drug-resistant pathogens. This study explored the immunomodulatory effects of co-expressing porcine interleukin 3, 7, and 15 in Yarrowia lipolytica, denoted as Po1h-IL-3\/7\/15. A 42-day experiment involving mouse immunization and pathogen challenge was conducted, during which in vivo assessments of antibodies, immune-related cells, and gene expression were detected following oral administration of Po1h-IL-3\/7\/15. Immunological alterations in mice were analyzed using flow cytometry, qRT-PCR, ELISA, and HE staining. Notably, the serum IgG and intestinal sIgA levels in the Po1h-IL-3\/7\/15 group were substantially elevated compared to the control groups (p &lt; 0.01), so were the contents of IL-7, IL-15, IFN-\u03b3, IL-22, IL-23, and TNF-\u03b1. Furthermore, there was a marked increase in na\u00efve T cells and central memory T cells, accompanied by a significant decrease in regulatory T cells in peripheral blood. Post-challenge with Staphylococcus aureus or Salmonella typhimurium, the expression levels of BD2, IL-1\u03b2, IL-8, Jak1, Reg\u2162, S100A8, STAT1, and TNF-\u03b1 genes in the intestines of the Po1h-IL-3\/7\/15 group were markedly higher than those in the control groups (p &lt; 0.01). Following the challenges, the survival rate of the Po1h-IL-3\/7\/15 group was 100%, a significant increase compared to the 20% and 40% survival rates observed in the control groups (p &lt; 0.05). These results confirm that IL-3\/7\/15 significantly boosts innate immunity, humoral and cell-mediated immune responses, and intestinal mucosal immunity in mice, enhancing resistance to bacterial infections and exhibiting potent protective effects.<\/jats:p>","DOI":"10.3390\/biology14040366","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T05:43:33Z","timestamp":1743572613000},"page":"366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Immunity and Infection Resistance in Mice Through Co-Expression of Porcine IL-3, IL-7, and IL-15 Fusion Molecules in Yarrowia lipolytica"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7303-2562","authenticated-orcid":false,"given":"Junjie","family":"Peng","sequence":"first","affiliation":[{"name":"College of Life Science, Sichuan University, Chengdu 610065, China"},{"name":"National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5172-2247","authenticated-orcid":false,"given":"Linhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangling","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan Animal Science Academy, Chengdu 610066, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebin","family":"Lv","sequence":"additional","affiliation":[{"name":"Sichuan Animal Science Academy, Chengdu 610066, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Animal Science Academy, Chengdu 610066, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-561X","authenticated-orcid":false,"given":"Jianlin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine, Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu 610500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3296-3015","authenticated-orcid":false,"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Life Science, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.14202\/vetworld.2021.210-221","article-title":"Antimicrobial Uses for Livestock Production in Developing Countries","volume":"14","author":"Hosain","year":"2021","journal-title":"Vet. World"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and Chemokines: At the Crossroads of Cell Signalling and Inflammatory Disease","volume":"1843","author":"Turner","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern Recognition Receptors and Inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"156268","DOI":"10.1016\/j.cyto.2023.156268","article-title":"Cytokines and Their Role as Immunotherapeutics and Vaccine Adjuvants: The Emerging Concepts","volume":"169","author":"Rahman","year":"2023","journal-title":"Cytokine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.1016\/j.vaccine.2020.08.054","article-title":"Adjuvants for Swine Vaccines: Mechanisms of Actions and Adjuvant Effects","volume":"38","author":"Charerntantanakul","year":"2020","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0165-2427(94)05301-8","article-title":"Influence of Recombinant Bovine Interleukin-1\u03b2 and Interleukin-2 in Pigs Vaccinated and Challenged with Streptococcus suis","volume":"44","author":"Blecha","year":"1995","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.rvsc.2005.07.009","article-title":"Effect of Transgenic Expression of Porcine Interleukin-6 Gene and CpG Sequences on Immune Responses of Newborn Piglets Inoculated with Pseudorabies Attenuated Vaccine","volume":"80","author":"Zhang","year":"2006","journal-title":"Res. Vet. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1165\/ajrcmb\/7.4.365","article-title":"Cytokine-Cytokine Interactions in the Context of Cytokine Networking","volume":"7","author":"Elias","year":"1992","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1093\/intimm\/13.7.897","article-title":"Mechanisms of Cytokine Synergy Essential for Vaccine Protection against Viral Challenge","volume":"13","author":"Ahlers","year":"2001","journal-title":"Int. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.4142\/jvs.2014.15.1.99","article-title":"Positive Effects of Porcine IL-2 and IL-4 on Virus-Specific Immune Responses Induced by the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) ORF5 DNA Vaccine in Swine","volume":"15","author":"Tang","year":"2014","journal-title":"J. Vet. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.immuni.2019.03.022","article-title":"GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation","volume":"50","author":"Dougan","year":"2019","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1399-3089.1997.tb00172.x","article-title":"Xenogeneic Bone Marrow Transplantation: I. Cloning, Expression, and Species Specificity of Porcine IL-3 and Granulocyte-Macrophage Colony-Stimulating Factor","volume":"4","author":"Hawley","year":"1997","journal-title":"Xenotransplantation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1016\/j.vaccine.2006.01.023","article-title":"Porcine Interleukin-3 Enhances DNA Vaccination against Classical Swine Fever","volume":"24","author":"Andrew","year":"2006","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, D., Tang, T.-X., Deng, H., Yang, X.-P., and Tang, Z.-H. (2021). Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.747324"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S0167-4781(00)00304-3","article-title":"cDNA Cloning and Expression of Swine IL-7 from Neonatal Intestinal Epithelium1","volume":"1517","author":"Ueha","year":"2001","journal-title":"Biochim. Biophys. Acta Gene Struct. Expr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.micinf.2011.10.006","article-title":"The Role of Interleukin-15 in Inflammation and Immune Responses to Infection: Implications for Its Therapeutic Use","volume":"14","author":"Perera","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1182\/blood.V89.1.201","article-title":"Interleukin-15 Triggers the Proliferation and Cytotoxicity of Granular Lymphocytes in Patients With Lymphoproliferative Disease of Granular Lymphocytes","volume":"89","author":"Zambello","year":"1997","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1002\/eji.200737772","article-title":"Historical Insights into Cytokines","volume":"37","author":"Dinarello","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/eji.201646723","article-title":"IL-17 and IL-22 in Immunity: Driving Protection and Pathology","volume":"47","author":"Eyerich","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/ni.2025","article-title":"Border Patrol: Regulation of Immunity, Inflammation and Tissue Homeostasis at Barrier Surfaces by IL-22","volume":"12","author":"Sonnenberg","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nm1720","article-title":"Interleukin-22 Mediates Early Host Defense against Attaching and Effacing Bacterial Pathogens","volume":"14","author":"Zheng","year":"2008","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1084\/jem.194.12.1711","article-title":"Cytokine-Driven Proliferation and Differentiation of Human Naive, Central Memory, and Effector Memory CD4+ T Cells","volume":"194","author":"Geginat","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_23","first-page":"474","article-title":"Treg Cells: A Potential Regulator for IL-22 Expression?","volume":"7","author":"Lin","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jeron, A., Hansen, W., Ewert, F., Buer, J., Geffers, R., and Bruder, D. (2012). ChIP-on-Chip Analysis Identifies IL-22 as Direct Target Gene of Ectopically Expressed FOXP3 Transcription Factor in Human T Cells. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-705"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev.iy.04.040186.002133","article-title":"Immunoglobulin A: Strategic Defense Initiative at the Mucosal Surface","volume":"4","author":"Underdown","year":"1986","journal-title":"Annu. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/mi.2007.6","article-title":"The Immune Geography of IgA Induction and Function","volume":"1","author":"Macpherson","year":"2008","journal-title":"Mucosal Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.immuni.2007.10.011","article-title":"Entry Route of Salmonella Typhimurium Directs the Type of Induced Immune Response","volume":"27","author":"Martinoli","year":"2007","journal-title":"Immunity"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/4\/366\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:08:20Z","timestamp":1760029700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/4\/366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,2]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["biology14040366"],"URL":"https:\/\/doi.org\/10.3390\/biology14040366","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2025,4,2]]}}}