NLRP3 inflammasome activation by particles and fibers: implications for human hazard assessment

Our plain-English summary of NLRP3 inflammasome activation by particles and fibers: implications for human hazard assessment, by M. Busch, G. Bredeck, H. Bouwmeester, et al (Archives of Toxicology, 2026).

The study

• Authors: M. Busch, G. Bredeck, H. Bouwmeester, R.P.F. Schins
• Journal: Archives of Toxicology
• Published: 2026;100(10):4299-4318
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome has been shown to be involved in the manifestation of adverse effects following exposure to occupational, dietary and environmental particulate matter. In this review, we summarize knowledge on NLRP3 inflammasome activation by particles and fibers in vitro and in vivo, outline dominant activation mechanisms and discuss the link to human diseases. While the association between NLRP3 activation and development of diseases is well established for occupational exposure to mineral dusts like asbestos and quartz, the health effects of low-level exposure to environmental particulate pollutants, such as micro- and nanoplastics, desert dust or novel nanocomposites remain to be unraveled. Based on the combined literature of well-studied and emerging particles, we emphasize the relevance of testing for NLRP3 activation in the hazard assessment of novel particulate materials.

© 2026. The Author(s).

In plain English

This article was a review, not a new study; the authors stated that no datasets were generated or analysed. It summarized cell and animal research on how particles and fibers activate the NLRP3 inflammasome, a protein complex found mainly in immune cells that is involved in inflammation. It also discussed links to human disease. Materials covered included asbestos fibers, crystalline silica, coal mine dust, titanium dioxide, micro- and nanoplastics and desert dust. The review described several asbestos findings from earlier studies. In macrophage models, asbestos fibers caused 'frustrated phagocytosis', where immune cells fail to fully engulf long fibers. Mice lacking NLRP3 showed decreased inflammation after 9-day asbestos inhalation. Mice lacking NLRP3 or caspase-1 showed less peritoneal wall thickening after asbestos exposure. In asbestos-exposed workers, some NLRP3 gene variants were reported to be associated with decreased and others with increased risk of asbestosis. The authors noted that direct human evidence was limited. They concluded that the NLRP3 and disease association is well established for occupational mineral dusts like asbestos and quartz. They emphasized testing for NLRP3 activation when assessing the hazard of novel particulate materials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published in vitro and in vivo studies; no new data were generated
• Who was studied: No study population of its own; the review drew on published literature about cell models, laboratory animals and some occupational studies of workers
• Exposure: A range of particles and fibers, including asbestos fibers (individual asbestos fiber types not named), crystalline silica (quartz and cristobalite), coal mine dust, titanium dioxide, micro- and nanoplastics and desert dust
• Main results:
  • The review described earlier studies reporting that asbestos fibers caused frustrated phagocytosis in macrophage models, leading to NLRP3 activation and IL-1β secretion
  • The review cited an earlier rodent study (Dostert et al. 2008) in which mice lacking NLRP3 showed decreased inflammatory parameters after 9-day inhalation of asbestos
  • The review cited an earlier study (Thompson et al. 2017) in which mice lacking NLRP3 or caspase-1 showed reduced thickening of the peritoneal walls and peritoneal submesothelium after asbestos exposure, compared with wildtype animals
  • The review cited earlier studies of workers occupationally exposed to asbestos. Depending on the variant, certain NLRP3 gene variants were associated with a decreased (Franko et al. 2020) or increased (Kukkonen et al. 2014) risk of asbestosis
  • The review noted that earlier studies linked the iron content of asbestos to the generation of reactive oxygen species
  • The authors reported that in their own earlier in vitro study (Busch et al. 2022a), selected micro- and nanoplastics showed no evidence of NLRP3 activation in macrophage-like cells; amino-modified polystyrene particles were the exception
• The authors' conclusion: The authors concluded that the association between NLRP3 activation and disease is well established for occupational exposure to mineral dusts such as asbestos and quartz. They concluded that the health effects of low-level environmental particles remain to be unraveled. They emphasized testing for NLRP3 activation in the hazard assessment of novel particulate materials.
• Limitations the authors state:
  • The authors stated that direct evidence of NLRP3 activation by particles in humans is limited, and that most available human data come from occupational epidemiological studies
  • The authors stated that when different studies are compared, the amount of IL-1β released in cell tests does not always match how hazardous a particle actually is

Topics

Medical terms in this study, explained in our Lexicon: Occupational Exposure.

Related studies

• Biological mechanisms of non-linear dose-response for respirable mineral fibers — L.A.T. Cox (2018)
• The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases — M. Sayan, B.T. Mossman (2016)
• The Synthetic Lignan Secoisolariciresinol Diglucoside Prevents Asbestos-Induced NLRP3 Inflammasome Activation in Murine Macrophages — R.A. Pietrofesa, P. Woodruff, et al. (2017)
• PKC/ROS-Mediated NLRP3 Inflammasome Activation Is Attenuated by Leishmania Zinc-Metalloprotease during Infection — M.T. Shio, J.G. Christian, et al. (2015)
• Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation — E. Meunier, A. Coste, et al. (2012)
• Vimentin regulates activation of the NLRP3 inflammasome — G. dos Santos, M.R. Rogel, et al. (2015)

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