Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation

Govind Gupta, Jasreen Kaur, Kunal Bhattacharya, Benedict J. Chambers, Arianna Gazzi, Giulia Furesi, Martina Rauner, Claudia Fuoco, Marco Orecchioni, Lucia Gemma Delogu, Lars Haag, Jan Eric Stehr, Aurélien Thomen, Romain Bordes, Per Malmberg, Gulaim A. Seisenbaeva, Vadim G. Kessler, Michael Persson, Bengt Fadeel

Research output: Contribution to journalArticlepeer-review


Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.

Original languageEnglish (US)
Pages (from-to)17451-17467
Number of pages17
JournalACS nano
Issue number17
StatePublished - Sep 12 2023


  • cell death
  • inflammasome
  • mass spectrometry
  • monocyte
  • silica nanoparticles

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy


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