The impact of cytomegalovirus coinfection on tuberculosis in the mouse model.

BACKGROUND: Tuberculosis (TB) remains a major global health challenge, with 10.6 million new cases and 1.3 million deaths annually. HIV coinfection is a well-known risk factor in high-burden regions, but emerging evidence suggests that other viral infections, including cytomegalovirus (CMV), may also impact TB pathogenesis. CMV is a ubiquitous herpesvirus capable of lifelong persistence, and its potential role in modulating TB progression remains unclear. METHODS: In this study, we established a murine coinfection model in C57BL/6 mice to investigate the effects of latent murine CMV (MCMV) on Mycobacterium tuberculosis (Mtb) infection. Mice were infected with either Mtb alone or with both Mtb and MCMV. Disease progression, mortality, bacterial load, viral clearance, and immune responses were assessed. RESULTS: Contrary to our hypothesis, latent MCMV infection improved disease outcomes and reduced mortality following Mtb infection. This effect was independent of bacterial control or viral clearance. Instead, coinfected mice exhibited a distinct immunological environment in the lungs, with elevated levels of inflammatory mediators (IL-1α, IL-1β, TNF, IFN-γ, CXCL9, CXCL10, CCL2) and altered immune cell composition. Lesions in the lungs of coinfected mice were organized differently compared to those infected with Mtb alone. Notably, introducing MCMV during an established Mtb infection led to enhanced disease progression, highlighting the importance of the timing and sequence of infections. CONCLUSION: Our findings demonstrate for the first time that latent MCMV infection can improve disease outcomes in Mtb-infected mice, suggesting that viral latency may modulate the immune response in a way that enhances host defense against tuberculosis.