Exposure to air pollution is associated with neurological diseases. Traffic is a major source of air pollution, consisting of a complex mixture of ultrafine particles, that can invade the brain and induce a microglia-mediated inflammatory response. However, the exact mechanisms of how traffic-related particles impact human microglia remain poorly understood. This study investigates the effects of diesel exhaust particles (DEPs) on human induced pluripotent stem cell-derived microglia-like cells (iMGL). We exposed iMGLs to three different DEPs and studied the impact on the iMGL transcriptome and functionality, focusing on cytokine secretion, mitochondrial respiration, lysosomal function, and phagocytosis. A20 particles were collected from a heavy-duty engine run with petroleum diesel. For A0, the same engine was run with renewable diesel. E6 was produced with a modern 2019 model diesel passenger car run with renewable diesel. RNAseq revealed activation of the cytokine storm pathway and inhibition of the autophagy pathway in iMGLs after exposure to particles derived from older diesel emission technology (A20, A0). Particles from the modern diesel engine technology (E6) did not alter microglial transcriptome after 24 h exposure. A20 and A0 exposure led to impaired lysosomal functions in iMGLs. In contrast, E6 did not cause major alterations in microglia functions. In addition, we show that response to particles is more pronounced in human iMGLs compared to mouse primary microglia. To conclude, particles from older emission technology impair phago-lysosomal functions of iMGLs, but modern alternatives with filtration do not induce drastic changes in the functionality of iMGLs.

A 1 Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland

A 1 Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland; Department of Biotechnology and Bioscience University of Milano Bicocca Milan Italy

Department of Biotechnology and Bioscience University of Milano Bicocca Milan Italy

Department of Environmental and Biological Science University of Eastern Finland Kuopio Finland

Department of Molecular Pharmacology Groningen Research Institute of Pharmacy Faculty of Science and Engineering University of Groningen the Netherlands

Department of Molecular Pharmacology Groningen Research Institute of Pharmacy Faculty of Science and Engineering University of Groningen the Netherlands; Department of Molecular Cell Biology and Immunology Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam the Netherlands

Department of Molecular Pharmacology Groningen Research Institute of Pharmacy Faculty of Science and Engineering University of Groningen the Netherlands; Groningen Research Institute for Asthma and COPD University of Groningen University Medical Center Groningen Groningen the Netherlands

Department of Toxicology and Molecular Epidemiology Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Electron Microscopy Unit Institute of Biotechnology Helsinki Institute of Life Science University of Helsinki Helsinki Finland

VTT Technical Research Centre of Finland Espoo Finland

Citace poskytuje Crossref.org