{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:01:12Z","timestamp":1781820072902,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["AGL2017-87415-R"],"award-info":[{"award-number":["AGL2017-87415-R"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["PID2022-142887OB-I00"],"award-info":[{"award-number":["PID2022-142887OB-I00"]}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science, Innovation and Universities","doi-asserted-by":"publisher","award":["AGL2017-87415-R"],"award-info":[{"award-number":["AGL2017-87415-R"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science, Innovation and Universities","doi-asserted-by":"publisher","award":["PID2022-142887OB-I00"],"award-info":[{"award-number":["PID2022-142887OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidad de Cordoba","award":["AGL2017-87415-R"],"award-info":[{"award-number":["AGL2017-87415-R"]}]},{"name":"Universidad de Cordoba","award":["PID2022-142887OB-I00"],"award-info":[{"award-number":["PID2022-142887OB-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The host response to S. Typhimurium infection can be post-transcriptionally regulated by miRNAs. In this study, we investigated the role of miR-215 using both in vivo porcine infection models and in vitro intestinal epithelial cell lines. Several miRNAs were found to be dysregulated in the porcine ileum during infection with wild-type and SPI2-defective mutant strains of S. Typhimurium, with some changes being SPI2-dependent. Notably, miR-215 was significantly downregulated during infection. To explore its functional role, gain-of-function experiments were performed by transfecting porcine intestinal epithelial cells (IPEC-J2) with a miR-215-5p mimic, followed by label-free quantitative (LFQ) proteomic analysis. This analysis identified 157 proteins, of which 35 were downregulated in response to miR-215 overexpression, suggesting they are potential targets of this miRNA. Among these, E2 small ubiquitin-like modifier (SUMO)-conjugating enzyme UBC9 and E3 ubiquitin-ligase HUWE1 were identified as key targets, both of which are upregulated during S. Typhimurium infection. The miR-215-mediated downregulation of these proteins resulted in a significant decrease in overall ubiquitination, a process crucial for regulating inflammasome activation and autophagy. Consistently, inflammasome markers caspase 1 (CASP1) and apoptosis-associated speck-like protein containing a CARD (ASC), as well as autophagy markers microtubule-associated protein 1A\/1B-light chain 3 (LC3B) and Ras-related protein Rab-11 (RAB11A), showed decreased expression in miR-215 mimic-transfected and infected IPEC-J2 cells. To further validate these findings, human intestinal epithelial cells (HT29) were used as a complementary model, providing additional insights into conserved immune pathways and extending the observations made in the porcine system. Overall, our findings demonstrate that miR-215 plays a significant role in modulating host inflammasome activation and autophagy by targeting proteins involved in ubiquitination during S. Typhimurium infection.<\/jats:p>","DOI":"10.3390\/ani15030431","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T05:55:22Z","timestamp":1738648522000},"page":"431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["miR-215 Modulates Ubiquitination to Impair Inflammasome Activation and Autophagy During Salmonella Typhimurium Infection in Porcine Intestinal Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Carmen","family":"Entrenas-Garc\u00eda","sequence":"first","affiliation":[{"name":"Immunogenomics and Molecular Pathogenesis Group, UIC Zoonosis and Emergent Diseases ENZOEM, Department of Genetics, University of Cordoba, 14014 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-2408","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Su\u00e1rez-C\u00e1rdenas","sequence":"additional","affiliation":[{"name":"Immunogenomics and Molecular Pathogenesis Group, UIC Zoonosis and Emergent Diseases ENZOEM, Department of Genetics, University of Cordoba, 14014 Cordoba, Spain"},{"name":"GA-14 Research Group, Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-0244","authenticated-orcid":false,"given":"Ra\u00fal","family":"Fern\u00e1ndez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Immunogenomics and Molecular Pathogenesis Group, UIC Zoonosis and Emergent Diseases ENZOEM, Department of Genetics, University of Cordoba, 14014 Cordoba, Spain"},{"name":"GA-14 Research Group, Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1685-8119","authenticated-orcid":false,"given":"Roc\u00edo","family":"Bautista","sequence":"additional","affiliation":[{"name":"Plataforma Andaluza de Bioinform\u00e1tica, Supercomputing and Bioinnovation Center (SCBI), Universidad de M\u00e1laga, 29590 Malaga, Spain"},{"name":"Institute of Biomedical Research in Malaga (IBIMA), IBIMA-RARE, 29590 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0112-3550","authenticated-orcid":false,"given":"M. Gonzalo","family":"Claros","sequence":"additional","affiliation":[{"name":"Plataforma Andaluza de Bioinform\u00e1tica, Supercomputing and Bioinnovation Center (SCBI), Universidad de M\u00e1laga, 29590 Malaga, Spain"},{"name":"Institute of Biomedical Research in Malaga (IBIMA), IBIMA-RARE, 29590 Malaga, Spain"},{"name":"Institute for Mediterranean and Subtropical Horticulture \u201cLa Mayora\u201d (IHSM-UMA-CSIC), 29590 Malaga, Spain"},{"name":"Department of Molecular Biology and Biochemistry, Universidad de M\u00e1laga, 29010 Malaga, Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) U741, 29071 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6592-2231","authenticated-orcid":false,"given":"Juan J.","family":"Garrido","sequence":"additional","affiliation":[{"name":"Immunogenomics and Molecular Pathogenesis Group, UIC Zoonosis and Emergent Diseases ENZOEM, Department of Genetics, University of Cordoba, 14014 Cordoba, Spain"},{"name":"GA-14 Research Group, Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5084-8999","authenticated-orcid":false,"given":"Sara","family":"Zald\u00edvar-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Immunogenomics and Molecular Pathogenesis Group, UIC Zoonosis and Emergent Diseases ENZOEM, Department of Genetics, University of Cordoba, 14014 Cordoba, Spain"},{"name":"GA-14 Research Group, Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority (EFSA), and European Centre for Disease Prevention and Control (ECDC) (2023). 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