BRIEF RESEARCH REPORT article
Front. Cardiovasc. Med.
Sec. General Cardiovascular Medicine
Antimicrobial Therapy Combined with C-C chemokine receptor type 2 (CCR2) Modulation Dampens Mycobacteria-Aggravated Monocyte Activation and Atherosclerosis
Rocio Egoavil-Espejo 1
April Haller 1
Manuel G Feria 1
Sanjay K Jain 2
Medha Singh 2
Joseph E Qualls 3
David Y Hui 4
Moises A Huaman 1
1. Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States
2. Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States
3. Department of Biological Sciences, Thomas More University, Crestview Hills, United States
4. Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, United States
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Abstract
Background: 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. Methods: Twelve-week-old low-density lipoprotein receptor knockout (Ldlr-/-) mice were infected with Mycobacterium bovis Bacille-Calmette-Guérin (BCG; 1.0–2.5 x106 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 Ldlr-/- 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. Results: Compared to uninfected mice, untreated BCG-infected mice and BCG-infected mice treated with INH/RIF exhibited an expansion of Ly6Clow 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. Conclusions: 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.
Summary
Keywords
atherosclerosis3, Cardiovascular5, CCR24, Mycobacteria1, tuberculosis2
Received
24 November 2025
Accepted
19 February 2026
Copyright
© 2026 Egoavil-Espejo, Haller, Feria, Jain, Singh, Qualls, Hui and Huaman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Moises A Huaman
Disclaimer
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