Immunomodulatory Effects of Subacute Inhalation Exposure to Copper Oxide Nanoparticles in House Dust Mite-Induced Asthma

It has been shownthat inhalation exposure to copperoxide nanoparticles(CuO NPs) results in pulmonary inflammation. However, immunomodulatoryconsequences after CuO NP inhalation exposure have been less explored.We tested the effect of CuO NP aerosols on immune responses in healthy,house dust mite (HDM) asthmatic, or allergen immunotherapy (AIT)-treatedasthmatic mice (BALB/c, females). The AIT consisted of a vaccine comprisingHDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatmentinvolved mice being immunized (via subcutaneous (sc) injection; 2doses) while concomitantly being exposed to CuO NP aerosols (overa 2 week period), starting on the day of the first vaccination. Micewere then sensitized twice by sc injection and subsequently challengedwith HDM extract 10 times by intranasal instillation. The asthmaticmodel followed the same timeline except that no immunizations wereadministered. All mice were necropsied 24 h after the end of the HDMchallenge. CuO NP-exposed healthy mice showed a significant decreasein T(H)1 and T(H)2 cells, and an elevation in T-bet(+) Treg cells, even 40 days after the last exposure to CuO NPs.Similarly, the CuO NP-exposed HDM asthma model demonstrated decreasedT(H)2 responses and increased T-bet(+) Treg cells.Conversely, CuO NP inhalation exposure to AIT-treated asthmatic miceresulted in an increase in T(H)2 cells. In conclusion, immunomodulatoryeffects of inhalation exposure to CuO NPs are dependent on immuneconditions prior to exposure.