{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:40:23Z","timestamp":1792651223290,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012648","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031445","name":"New Jersey Commission on Cancer Research","doi-asserted-by":"crossref","award":["COCR22RBG005"],"award-info":[{"award-number":["COCR22RBG005"]}],"id":[{"id":"10.13039\/100031445","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["R01HL134870"],"award-info":[{"award-number":["R01HL134870"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> is a versatile bacterium responsible for conditions ranging from mild skin and soft-tissue infections to serious disorders such as pneumonia and sepsis. Monocytes play a role in protection against pathogens by migrating to inflamed tissues and differentiating into macrophages but their specific role in the context of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> pulmonary infection has not been fully elucidated. Using a CCR2-DTR transgenic mouse model we demonstrate that over the course of infection monocyte depletion resulted in worse airway clearance of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>. The bronchoalveolar lavage fluid (BALF) of CCR2-DTR mice after <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> infection displayed significant decreases in interleukin-12 (IL-12), IFN-\u03b3, IP-10, MIG and RANTES, all IFN-\u03b3 regulated, compared to wild-type (WT) infected controls. NK cells were identified as the main producers of IFN-\u03b3, but both NK cells and IFN-\u03b3 were dispensable for clearance. We demonstrated through cytokine production and RNA-seq analysis that IL-12 and IL-12 regulated genes are strongly induced in monocytes upon <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> infection. Administration of IL-12 during infection restored the bacterial burdens in the BALF and lungs of monocyte-depleted CCR2-DTR mice to the levels of WT mice, independent of IFN-\u03b3. In the absence of monocytes, alveolar macrophages are the primary phagocytic cells, and IL-12 influences their capacity to produce reactive oxygen species and clear <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>. These results show that production of IL-12 contributes to the control of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> via its influence on alveolar macrophage function.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012648","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T17:37:13Z","timestamp":1729186633000},"page":"e1012648","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Monocyte-regulated interleukin 12 production drives clearance of Staphylococcus aureus"],"prefix":"10.1371","volume":"20","author":[{"given":"Adeline","family":"Peignier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lemenze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7304-3392","authenticated-orcid":true,"given":"Dane","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ppat.1012648.ref001","volume-title":"Antibiotic Resistance Threats in the United 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