Think Beyond Particle Cytotoxicity: When Self-Cellular Components Released After Immunogenic Cell Death Explain
Riccardo Leinardi1, Chiara Longo Sanchez-Calero1, François Huaux1
1Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Bruxelles, Belgium.
Abstract:
The prolonged perturbation of the immune system following the release of a plethora of self-molecules (known as damage-associated molecular patterns, DAMPs) by stressed or dying cells triggers acute and chronic pathological responses. DAMPs are commonly released after plasma membrane damage or complete rupture due to immunogenic cell death (ICD), upon numerous stressors including infectious and toxic agents. The set of DAMPs released after ICD include mature proinflammatory cytokines and alarmins, but also polymeric macromolecules. These self-intracellular components are recognized by injured and healthy surrounding cells via innate receptors, and induce upregulation of stress-response mechanisms, including inflammation. In this review, by overstepping the simple toxicological evaluation, we apply ICD and DAMP concepts to silica cytotoxicity, providing new insights on the mechanisms driving the progress and/or the exacerbation of certain SiO2-related pathologies. Finally, by proposing self-DNA as new crucial DAMP, we aim to pave the way for the development of innovative and easy-to-perform predictive tests to better identify the hazard of fine and ultrafine silica particles. Importantly, such mechanisms could be extended to nano/micro plastics and diesel particles, providing strategic advice and reports on their health issues.
Insights
Cell damage releases damage-associated molecular patterns (DAMPs), triggering immune responses. This review applies immunogenic cell death (ICD) and DAMP concepts to silica, proposing self-DNA as a key DAMP for hazard detection.
Area of Science:
- Immunotoxicology
- Cellular Stress Response
- Nanotoxicology
Background:
- Prolonged immune system perturbation by damage-associated molecular patterns (DAMPs) from stressed cells causes pathological responses.
- DAMPs, including cytokines and alarmins, are released upon cell damage, notably immunogenic cell death (ICD), activating innate immune receptors and inflammation.
- Silica (SiO2) exposure is linked to pathologies, but underlying mechanisms require deeper investigation.
Purpose of the Study:
- To apply immunogenic cell death (ICD) and damage-associated molecular pattern (DAMP) concepts to understand silica cytotoxicity.
- To provide novel insights into the mechanisms driving silica-related pathologies.
- To propose self-DNA as a critical DAMP for developing predictive hazard tests for silica particles.
Main Methods:
- Review of existing literature on DAMPs, ICD, and silica toxicology.
- Application of ICD and DAMP frameworks to analyze silica cytotoxicity.
- Identification of potential DAMPs, including self-DNA, in silica-induced cellular responses.
Main Results:
- Silica cytotoxicity can be better understood through the lens of ICD and DAMP release.
- Self-intracellular components, particularly self-DNA, are proposed as key DAMPs in silica-related pathologies.
- The proposed mechanisms offer a basis for developing predictive tests for silica particle hazards.
Conclusions:
- The ICD and DAMP paradigm offers a novel perspective on silica cytotoxicity and related diseases.
- Self-DNA emerges as a significant DAMP for assessing the hazards of fine and ultrafine silica particles.
- These insights can be extended to other particulate materials like nano/microplastics and diesel exhaust particles.
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