Early-life long-term exposure to ZnO nanoparticles suppresses innate immunity regulated by SKN-1/Nrf and the p38 MAPK signaling pathway in Caenorhabditis elegans
Journal
Environmental Pollution
Journal Volume
256
Date Issued
2020
Author(s)
Abstract
Early-life long-term ZnO-NPs exposure suppresses innate immunity, leading to potential negative impacts on human health. ? 2019 Elsevier LtdThe widespread use of zinc oxide nanoparticles (ZnO-NPs) has led to their release into the environment, and they thus represent a potential risk for both humans and ecosystems. However, the negative impact of ZnO-NPs on the immune system, especially in relation to host defense against pathogenic infection and its underlying regulatory mechanisms, remains largely unexplored. This study investigated the effects of early-life long-term ZnO-NPs exposure (from L1 larvae to adults) on innate immunity and its underlying mechanisms using a host–pathogen Caenorhabditis elegans model, and this was compared with the effect of ionic Zn. The results showed that the ZnO-NPs taken up by C. elegans primarily accumulated in the intestine and that early-life long-term ZnO-NPs exposure at environmentally relevant concentrations (50 and 500 μg/L) decreased the survival of wild-type C. elegans when faced with pathogenic Pseudomonas aeruginosa PA14 infection. Early-life long-term ZnO-NPs (500 μg/L) exposure significantly increased (by about 3-fold) the accumulation of live P. aeruginosa PA14 colonies in the intestine of C. elegans. In addition, ZnO-NPs (500 μg/L) inhibited the intestinal nuclear translocation of SKN-1 and also downregulated gcs-1 gene expression, which is an SKN-1 target gene. Further evidence revealed that early-life long-term exposure to ZnO-NPs (500 μg/L) did not increase susceptibility to mutation among the genes (pmk-1, sek-1, and nsy-1) encoding the p38 mitogen-activated protein kinase (MAPK) cascade in response to P. aeruginosa PA14 infection, though ZnO-NPs significantly decreased the mRNA levels of pmk-1, sek-1, and nsy-1. This study provides regulatory insight based on evidence that ZnO-NPs suppress the innate immunity of C. elegans and highlights the potential health risks of certain environmental nanomaterials, including ZnO-NPs, in terms of their immunotoxicity at environmentally relevant concentrations. ? 2019 Elsevier Ltd
Subjects
Caenorhabditis elegans; Early-life long-term exposure; Innate immunity; p38 MAPK pathway; SKN-1; Zinc oxide nanoparticles (ZnO-NPs)
SDGs
Other Subjects
Gene expression; Health risks; II-VI semiconductors; Immune system; Nanoparticles; Zinc oxide; Caenorhabditis elegans; Innate immunity; Long term exposure; P38 MAPK; SKN-1; ZnO nanoparticles; messenger RNA; mitogen activated protein kinase p38; Nrf protein; transcription factor; zinc chloride; zinc oxide nanoparticle; Caenorhabditis elegans protein; DNA binding protein; mitogen activated protein kinase p38; nanoparticle; skn-1 protein, C elegans; transcription factor; zinc oxide; bioaccumulation; concentration (composition); environmental assessment; genetic marker; host-pathogen interaction; immunity; innate behavior; nanoparticle; nematode; pollution exposure; toxicity; zinc; adult; animal experiment; animal model; bacterial gene; bacterial virulence; bacterium colony; bioaccumulation; Caenorhabditis elegans; concentration (parameter); controlled study; down regulation; gcs 1 gene; gene expression regulation; gene mutation; gene targeting; genetic susceptibility; health hazard; host pathogen interaction; immunotoxicity; innate immunity; larva; long term exposure; nonhuman; nsy 1 gene; pmk 1 gene; Pseudomonas aeruginosa; Pseudomonas infection; sek 1 gene; signal transduction; SKN 1 gene; survival rate; wild type; animal; drug effect; ecosystem; growth, development and aging; immunology; innate immunity; MAPK signaling; metabolism; microbiology; Caenorhabditis elegans; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; DNA-Binding Proteins; Ecosystem; Immunity, Innate; MAP Kinase Signaling System; Nanoparticles; p38 Mitogen-Activated Protein Kinases; Pseudomonas aeruginosa; Transcription Factors; Zinc Oxide
Type
journal article