Antimicrobial therapy combined with C-C chemokine receptor type 2 modulation dampens mycobacteria-aggravated monocyte activation and atherosclerosis

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: 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: 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.