{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:27:09Z","timestamp":1777890429554,"version":"3.51.4"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Bovine mastitis remains one of the most prevalent diseases in dairy cattle and is largely managed through antibiotic therapy, which contributes to antimicrobial resistance. Host-directed strategies that enhance mammary epithelial defenses may complement conventional treatments. Although vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      metabolites can modulate immune responses, their comparative effects on bovine mammary epithelial cells have not been fully characterized. This study compared the antimicrobial and host-directed effects of vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      (D), 25-hydroxyvitamin D\n                      <jats:sub>3<\/jats:sub>\n                      (25D), and 1\u03b1,25-dihydroxyvitamin D\n                      <jats:sub>3<\/jats:sub>\n                      (1,25D) through an integrated\n                      <jats:italic>in vitro<\/jats:italic>\n                      approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Antimicrobial and antibiofilm activity were assessed against mastitis-associated\n                      <jats:italic>Staphylococcus<\/jats:italic>\n                      spp. isolates. Bovine mammary epithelial MAC-T cells were then treated to evaluate cellular tolerance, transcriptional regulation of vitamin D-related enzymes and receptors, global proteomic alterations, and\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      internalization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      D and 25D were well tolerated by MAC-T cells. They exhibited limited antimicrobial or antibiofilm activity, but pretreatment of the cells with 25D significantly reduced\n                      <jats:italic>S. aureus<\/jats:italic>\n                      internalization. Enzymes involved in vitamin D metabolism were differentially regulated by 25D and 1,25D: while 24-hydroxylase was upregulated, vitamin D receptor expression remained largely unchanged. Proteomic profiling identified 2,203 proteins common to all conditions, as well as compound-specific signatures related to epithelial homeostasis, innate immunity, vitamin D catabolism, vesicular trafficking, endocytic processes, and mitochondrial organization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The findings indicate that vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      metabolites primarily act through host-directed mechanisms rather than by direct antimicrobial activity. They could thus potentially be used as complementary strategies to manage mastitis in alignment with One Health principles.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1815096","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:37:30Z","timestamp":1777613850000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D metabolites reshape bovine mammary epithelial responses relevant to mastitis through host-directed mechanisms"],"prefix":"10.3389","volume":"16","author":[{"given":"Georgina","family":"Tiraboschi","sequence":"first","affiliation":[{"name":"Instituto Multidisciplinario de Investigaci\u00f3n y Transferencia Agroalimentaria y Biotecnol\u00f3gica (IMITAB Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas - Universidad Nacional Villa Mar\u00eda (CONICET-UNVM))","place":["Villa Mar\u00eda, Argentina"]},{"name":"Instituto Acad\u00e9mico Pedag\u00f3gico de Ciencias B\u00e1sicas y Aplicadas, Universidad Nacional Villa Mar\u00eda (UNVM)","place":["Villa Mar\u00eda, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilina","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Facultad de Ciencias Exactas, F\u00edsico-Qu\u00edmicas y Naturales, Universidad Nacional de R\u00edo Cuarto (UNRC)","place":["R\u00edo Cuarto, Argentina"]},{"name":"Instituto de Biotecnolog\u00eda Ambiental y Salud (INBIAS-CONICET)","place":["R\u00edo Cuarto, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Isaac","sequence":"additional","affiliation":[{"name":"Instituto Multidisciplinario de Investigaci\u00f3n y Transferencia Agroalimentaria y Biotecnol\u00f3gica (IMITAB Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas - Universidad Nacional Villa Mar\u00eda (CONICET-UNVM))","place":["Villa Mar\u00eda, Argentina"]},{"name":"Instituto Acad\u00e9mico Pedag\u00f3gico de Ciencias B\u00e1sicas y Aplicadas, Universidad Nacional Villa Mar\u00eda (UNVM)","place":["Villa Mar\u00eda, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Laura","family":"Breser","sequence":"additional","affiliation":[{"name":"Instituto Multidisciplinario de Investigaci\u00f3n y Transferencia Agroalimentaria y Biotecnol\u00f3gica (IMITAB Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas - Universidad Nacional Villa Mar\u00eda (CONICET-UNVM))","place":["Villa Mar\u00eda, Argentina"]},{"name":"Instituto Acad\u00e9mico Pedag\u00f3gico de Ciencias B\u00e1sicas y Aplicadas, Universidad Nacional Villa Mar\u00eda (UNVM)","place":["Villa Mar\u00eda, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Porporatto","sequence":"additional","affiliation":[{"name":"Instituto Multidisciplinario de Investigaci\u00f3n y Transferencia Agroalimentaria y Biotecnol\u00f3gica (IMITAB Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas - Universidad Nacional Villa Mar\u00eda (CONICET-UNVM))","place":["Villa Mar\u00eda, Argentina"]},{"name":"Instituto Acad\u00e9mico Pedag\u00f3gico de Ciencias B\u00e1sicas y Aplicadas, Universidad Nacional Villa Mar\u00eda (UNVM)","place":["Villa Mar\u00eda, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana Paola","family":"Bohl","sequence":"additional","affiliation":[{"name":"Instituto Multidisciplinario de Investigaci\u00f3n y Transferencia Agroalimentaria y Biotecnol\u00f3gica (IMITAB Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas - Universidad Nacional Villa Mar\u00eda (CONICET-UNVM))","place":["Villa Mar\u00eda, Argentina"]},{"name":"Instituto Acad\u00e9mico Pedag\u00f3gico de Ciencias B\u00e1sicas y Aplicadas, Universidad Nacional Villa Mar\u00eda (UNVM)","place":["Villa Mar\u00eda, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"W547","DOI":"10.1093\/nar\/gkaf394","article-title":"The UniProt website API: facilitating programmatic access to protein knowledge","volume":"53","author":"Ahmad","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.3168\/jds.S0022-0302(96)76454-8","article-title":"Staphylococcus aureus invasion of bovine mammary epithelial cells","volume":"79","author":"Almeida","year":"1996","journal-title":"J. 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