PO4 - Airway exposure to micro- and nanoplastics induces macrophage activation and sarcoidosis-like granulomatous inflammation in mice
Lieke de Jong (Netherlands)1; Vicky Bogaard (Netherlands)1; Ingrid Bergen (Netherlands)1; Barbro Melgert (Netherlands)2; Elena Höppener (Netherlands)3; Ingeborg Kooter (Netherlands)3; Agnes Boots (Netherlands)4; Rudi Hendriks (Netherlands)1; Odilia Corneth (Netherlands)1; Jelle Miedema (Netherlands)1;
1 - Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; 2 - Department of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; 3 - Department of Environmental Modelling, Sensing & Analysis, TNO, Utrecht, the Netherlands; 4 - Department of Respiratory Toxicology, University of Maastricht, Maastricht, the Netherlands;
Keywords: Granuloma formation; Trigger; Micro- and Nanoplastics;
Select the theme: Genetics and Immunopathology: Advances in Contemporary Understanding and Prospects for Future Research
Type: Original Papers
Presentation: Poster Presentation

Introduction: Sarcoidosis is a granulomatous disease of unknown etiology, likely driven by a variety of triggers in genetically susceptible individuals. Common exposures associated with sarcoidosis include inorganic dusts, metals and silica, but the contribution of emerging airborne pollutants remains unclear. Micro- and nanoplastics (MNPs) are increasingly detected in air and human lung tissue and may act as novel environmental disease triggers. Upon inhalation, MNPs interact with immune cells, particularly tissue-resident macrophages, which are central to granuloma formation. However, the capacity of MNPs to induce granulomatous inflammation and the underlying macrophage-driven mechanisms remain poorly defined.

Objectives: To determine whether airway exposure to MNPs induces granulomatous inflammation in vivo and to characterize MNP-induced transcriptional responses in human macrophages.

Materials and Methods: C57BL/6J mice were intratracheally exposed to environmentally degraded polystyrene MNPs (<20 µm) once or daily for three consecutive days. Lung histology was assessed at days 1, 7 and 14, and immune cell infiltration was analyzed by flow cytometry. Additionally, human peripheral blood monocyte-derived macrophages (MDMs) were exposed to MNPs for 2 and 16 hours, followed by transcriptome analysis.

Results: Single MNP exposure induced acute lung inflammation, peaking at day 7. Histology revealed the formation of cellular aggregates that could be classified as granulomas based on the presence of CD11c+ myeloid cells and multinucleated giant cells, surrounded by CD3+ T cells (Figure 1A). Repeated exposure enhanced granulomatous inflammation (Figure 1B). Flow cytometry revealed an influx of myeloid cells and CD4⁺ T cells in the lungs.

In MDMs, MNP exposure induced rapid pro-inflammatory activation at 2 hours, including upregulation of Tnf and Ccl2, followed by a sustained inflammatory and stress-associated activation gene expression signature at 16 hours (Figure 1C-D).

Conclusions: Airway MNP exposure induces transient granulomatous inflammation and MDM activation programs in mice resembling key features of sarcoidosis in human. Further research should investigate MNPs as potential environmental triggers of sarcoidosis.

Figure 1