Zinc Oxide Nanoparticles Impair Bacterial Clearance by Macrophages

Abstract

The extensive development of nanoparticles (NPs) and their widespread employment in daily life have led to an increase in environmental concentrations of substances that may pose a biohazard to humans. The aim of this work was to examine the effects of zinc oxide nanoparticles (ZnO-NPs) on the host's pulmonary immune system response to nontypeable Haemophilus influenzae (NTHi) infection. A murine infection model was employed to assess pulmonary inflammation and bacterial clearance in response to exposure to ZnO-NPs. The molecular mechanisms underlying ZnO-NP-impaired macrophage activation were investigated. Treatment with ZnO-NPs impaired macrophage activation, leading to a delay in NTHi clearance in the bronchial alveolar lavage fluids and lungs. Exposure to ZnO-NPs followed by NTHi challenge decreased levels of nitric oxide compared with NTHi infection alone. The effects of ZnO-NPs involved downregulation of NTHi-activated expression of inducible nitric oxide synthase and the translocation of active NF-kB into the nucleus. These results demonstrate that exposure to ZnO-NPs can impair innate immune responses and attenuate macrophage responses to bacterial infection.