{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:20:55Z","timestamp":1783621255744,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014403","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000}}],"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yunnan International Joint Laboratory for Exploration and Utilization of Aromatic Chinese Medicinal Materials in Agriculture","award":["202503AP140024"],"award-info":[{"award-number":["202503AP140024"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372961"],"award-info":[{"award-number":["32372961"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32272955"],"award-info":[{"award-number":["32272955"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32472984"],"award-info":[{"award-number":["32472984"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Undergraduate Innovation Research Project","award":["202510183382"],"award-info":[{"award-number":["202510183382"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    As a common opportunistic pathogen,\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ) can rapidly adapt to the host immune system and cause chronic infections. Currently, such chronic infections are extremely difficult to eliminate, severely impairing the function of tissues and organs. We observed localized tissue senescence in the mammary glands of mice with chronic\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infection; however, the mechanism driving this senescence remains unclear. To address this, we employed a mouse model of chronic\n                    <jats:italic>S. aureus<\/jats:italic>\n                    -induced mastitis and an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of mouse mammary epithelial cells (mMECs) to confirm the inductive effect of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    on tissue and cellular senescence. Through integrated analysis of the transcriptome and metabolome of mouse mammary tissues, it was found that the ornithine cycle was significantly disordered following\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infection, wherein Arginase 1 (Arg1) serves as a key metabolic regulator. Notably, stimulation by\n                    <jats:italic>S. aureus<\/jats:italic>\n                    induces mammary epithelial cells to produce cytokines, thereby promoting the massive release of Arg1 by macrophages into the microenvironment, which constitutes one of the sources of abnormally elevated Arg1 in mammary tissue. This extracellular Arg1 is subsequently taken up by mammary epithelial cells, further accelerating the intracellular conversion of arginine to ornithine. The accumulation of ornithine and its downstream metabolites drives the occurrence of senescence in epithelial cells. Importantly, supplementation with excess arginine or ornithine can mimic this senescence phenotype, while knocking down Arg1 in epithelial cells can reverse this phenomenon. In summary, this study reveals a novel immunometabolic cross-regulation mechanism, specifically that Arg1 released by macrophages\u2014triggered by mammary epithelial cells under\n                    <jats:italic>S. aureus<\/jats:italic>\n                    stimulation\u2014acts as a paracrine senescence-inducing factor that acts back on mammary epithelial cells. The Arg1\u2014ornithine axis holds promise as a potential therapeutic target for chronic infection-associated tissue senescence.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014403","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T17:51:35Z","timestamp":1783360295000},"page":"e1014403","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Staphylococcus aureus rewires arginine metabolism to drive mammary aging via macrophage\u2013epithelial 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