Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia

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.

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Publication Details

Journal
Environment International
Published
2025-05-01
DOI
https://doi.org/10.1016/j.envint.2025.109467
Citations
6
Primary Topic
Neuroinflammation and Neurodegeneration Mechanisms
Type
article
Field-Weighted Citation Impact
5.05

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Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia

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6 citations
Environment International
Neuroinflammation and Neurodegeneration Mechanisms
5.05
article

Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia

Ilya Belevich, Táňa Závodná, Eija Jokitalo, Mari‐Anna Väänänen, Luca Giudice, Pasi Jalava, Katja M. Kanninen, Elisa Perciballi, Daniela Ferrari, Paula Korhonen, Liudmila Saveleva, Alejandra Sierra, Mireia Gómez‐Budia, Henna Jäntti, Mathias V. Schmidt, Amalia M. Dolga, Jan Topinka, Jari Koıstınaho, Päivi Aakko-Saksa, Tarja Malm, Anastasia Shakirzyanova, Angélica María Sabogal-Guáqueta, Šárka Lehtonen, Sohvi Ohtonen, Hong Yan, Ahmed Mohamed, Zdeněk Krejčík, Minna-Mari Tervo, Ashley Rillo-Albert
article en
6 citations

Abstract

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.

Environment InternationalVol. 199
University of Helsinki (FI), University of Eastern Finland (FI), Czech Academy of Sciences (CZ), Czech Academy of Sciences, Institute of Experimental Medicine (CZ), University of Milano-Bicocca (IT), VTT Technical Research Centre of Finland (FI)
Itä-Suomen Yliopisto, Helsingin Yliopisto, European Commission, University of Melbourne, Ministerstvo Školství, Mládeže a Tělovýchovy, Academy of Finland, Päivikki ja Sakari Sohlbergin Säätiö, Biocenter Finland, Horizon 2020 Framework Programme, Horizon 2020, H2020 Marie Skłodowska-Curie Actions
Openalex Percentile: Top 5%
Neuroinflammation and Neurodegeneration Mechanisms
5.05
DOIOpen Access PDFOpenAlex
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