{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:05:40Z","timestamp":1774940740407,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["R03TR004097"],"award-info":[{"award-number":["R03TR004097"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL156779"],"award-info":[{"award-number":["1R01HL156779"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tuberculosis is associated with increased risk of cardiovascular events. We investigated the impact of antimicrobial therapy alone and in combination with anti-CCR2 modulation in monocyte profiling and atherosclerosis development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twelve-week-old low-density lipoprotein receptor knockout (\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice were infected with\n                      <jats:italic>Mycobacterium bovis<\/jats:italic>\n                      Bacille-Calmette-Gu\u00e9rin (BCG; 1.0\u20132.5\u2009\u00d7\u200910\n                      <jats:sup>6<\/jats:sup>\n                      colony-forming units) via the intranasal route and fed a western-type high-fat diet for 16 weeks. Mice were treated with oral isoniazid and rifampin (INH\/RIF) between weeks 4 and 12 to induce microbiologic clearance, with and without intraperitoneal injections of anti-CCR2 monoclonal antibodies administered twice weekly. Age-matched infected and uninfected\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice served as controls. We assessed monocyte phenotyping using flow cytometry, and quantified atherosclerosis in aortas using Oil-Red-O staining. Plaque composition was assessed in aortic roots.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to uninfected mice, untreated BCG-infected mice and BCG-infected mice treated with INH\/RIF exhibited an expansion of Ly6C\n                      <jats:sup>low<\/jats:sup>\n                      non-classical monocytes, as well as increased expression of monocyte activation markers. BCG-infected mice developed increased atherosclerotic lesions in their aortae, regardless of INH\/RIF treatment. The addition of anti-CCR2 adjunctive therapy to INH\/RIF treatment decreased monocyte activation markers including MHC-II, CD64, CD36, CX3CR1, and diminished interleukin-6 production upon lipopolysaccharide stimulation. Finally, anti-CCR2 adjunctive therapy decreased atherosclerosis lesions of BCG-infected INH\/RIF-treated mice, while also decreasing plaque size and lipid content.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Monocyte activation and atherosclerosis burden remained elevated after BCG clearance with antimicrobials. The addition of anti-CCR2 to antimicrobial therapy dampened monocyte activation and atherosclerosis development. Our results indicate that combining antimicrobials with CCR2 immunomodulation may reduce mycobacteria-aggravated atherosclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1753414","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:33:51Z","timestamp":1774935231000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antimicrobial therapy combined with C-C chemokine receptor type 2 modulation dampens mycobacteria-aggravated monocyte activation and atherosclerosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Rocio","family":"Egoavil-Espejo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Cincinnati College of Medicine","place":["Cincinnati, OH, United 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