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Immunomodulatory Effects of Subacute Inhalation Exposure to Copper Oxide Nanoparticles in House Dust Mite-Induced Asthma
Journal article   Open access   Peer reviewed

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

Sudartip Areecheewakul, Andrea Adamcakova-Dodd, Zeb R. Zacharias, Xuefang Jing, David K. Meyerholz, Kevin L. Legge, Jon C. D. Houtman, Patrick T. O’Shaughnessy, Peter S. Thorne and Aliasger K. Salem
ACS nano, Vol.17(15), pp.14586-14603
07/18/2023
DOI: 10.1021/acsnano.3c01668
PMCID: PMC10416562
PMID: 37463491
url
https://doi.org/10.1021/acsnano.3c01668View
Published (Version of record) Open Access

Abstract

It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences 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)-treated asthmatic mice (BALB/c, females). The AIT consisted of a vaccine comprising HDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatment involved mice being immunized (via subcutaneous (sc) injection; 2 doses) while concomitantly being exposed to CuO NP aerosols (over a 2 week period), starting on the day of the first vaccination. Mice were then sensitized twice by sc injection and subsequently challenged with HDM extract 10 times by intranasal instillation. The asthmatic model followed the same timeline except that no immunizations were administered. All mice were necropsied 24 h after the end of the HDM challenge. CuO NP-exposed healthy mice showed a significant decrease in TH1 and TH2 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 decreased TH2 responses and increased T-bet+ Treg cells. Conversely, CuO NP inhalation exposure to AIT-treated asthmatic mice resulted in an increase in TH2 cells. In conclusion, immunomodulatory effects of inhalation exposure to CuO NPs are dependent on immune conditions prior to exposure.
Immunotherapy copper oxide nanoparticles immunomodulatory effects inhalation pulmonary toxicity house dust mite asthma model UIOWA OA Agreement

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