Immunosuppressive effects of early-life exposure to combustion-derived particulate matter: implications for enhanced severity due to respiratory tract infections (P3218)

Abstract

Abstract The association of elevated levels of ambient particulate matter with increased morbidity and mortality due to respiratory tract infections has been well documented. Interestingly, infants and young children appear to be the most vulnerable to these adversities. Using mice to model early-life exposure to combustion-derived particulate matter (CDPM), we demonstrate the development of an immunosuppressive environment in the lung as evidenced by increases in tolerogenic dendritic cells, regulatory T cells (Tregs), and IL-10 production and impairment of T effector proliferation in response to antigen. Specifically, infant mice co-exposed to CDPM and house dust mite allergen failed to develop certain hallmarks of asthma (e.g. airway hyperresponsiveness, eosinophilia, Th2 inflammation) while maintaining others (e.g. increased mucus production, elevated serum IgE). To investigate the effects of CDPM-induced immunosuppression on viral infections, exposed neonatal mice were infected with influenza (H1N1). CDPM-exposed and infected mice had significantly reduced pulmonary cytotoxic/helper T cell effector responses (Tc1, Tc2, Tc17/Th1, Th2; respectively) and significantly elevated Tregs compared to unexposed and infected mice. Consequently, this impairment in effector responses led to increased viral loads in the lungs of CDPM-exposed mice. Our data suggest a mechanism of exposure-mediated modulation of pulmonary disease in infants.