Abstract Carbonaceous nanoparticles (CNPs) are becoming increasingly prevalent due to industrial use and emissions from combustion and have emerged as exacerbators of chronic lung diseases. We have previously shown in mice, that CNPs can act as a "second hit", reactivating latent murine γ-herpesvirus 68 (MHV-68), a model for human herpesviruses endemic in all populations. In the lungs, CNPs were seen to activate MAPK signalling in infiltrating CD11b⁺ macrophages, creating an environment favouring viral reactivation. Additionally, repeated pulmonary CNP exposure promoted CD8⁺ T cell recruitment, T-cell proliferation and IFN-γ release following viral reactivation, with persistent T-cell activity. CNPs were also shown to cause epithelial injury, disrupting the alveolar barrier. However, the mechanisms by which CNPs promote macrophage-dependent T cell activation, driving cytotoxic epithelial injury through viral reactivation is poorly known. To address this, we combine bulk RNA-seq analysis, CycIF, cytokine assays, and in vitro co-cultures. Accordingly, this will enable us to profile T cell activation and differentiation during CNP exposure and viral reactivation, map cytokine production and T cell–macrophage interactions in lung tissue, examine molecular signalling and reactivation mechanisms, assess tissue damage and inflammation, and determine how T cell depletion influences immune responses and lung pathology. This work aims to elucidate interactions between environmental nanoparticles and latent viruses in chronic lung injury, potentially uncovering therapeutic targets for virus-driven exacerbations of lung diseases.
Kuruppu et al. (2026) studied this question.