Alveolar macrophages initiate the spatially targeted recruitment of neutrophils after nanoparticle inhalation
Lung resident immune cells are essential for initiating defenses against inhaled air pollutants, including nanoparticles (NPs), which contribute to pulmonary disease progression. Here, lung intravital microscopy was used to examine the pulmonary innate immune responses in mice, during acute aerosol exposure to carbon NPs, a common environmental pollutant, or fluorescent quantum dot NPs. We found that inhaled NPs triggered rapid, neutrophil recruitment, localized to alveolar NP deposition hotspots, orchestrated by alveolar macrophages (AMs) through both their motility and phagocytic activity. AM motility inhibition in the alveoli via intercellular adhesion molecule-1/LFA-1 blockade reduced neutrophil recruitment, as did impaired AM phagocytosis through C5a receptor 1/Fc-γ receptor I inhibition or by stealth NP surfaces. In addition, cellular degranulation inhibition indicated the importance of spatially focused cytokine release in neutrophil recruitment. Collectively, our study elucidates AM-epithelial interactions as a critical key event for NPs triggered neutrophilia, with AM motility and phagocytosis driving recruitment and site-specific immune responses in the alveolar microenvironment.
Authors
- Qiongliang Liu (ORCID: https://orcid.org/0009-0000-6113-6057)
- Dagmar Zeuschner (ORCID: https://orcid.org/0000-0002-6712-0192)
- Judith Secklehner (ORCID: https://orcid.org/0000-0003-0005-3535)
- Markus Rehberg (ORCID: https://orcid.org/0000-0001-7314-6332)
- Andreas Schröppel
- Qiaoxia Zhou (ORCID: https://orcid.org/0000-0001-6644-8391)
- Otmar Schmid (ORCID: https://orcid.org/0000-0002-8012-7786)
- Leo M. Carlin (ORCID: https://orcid.org/0000-0001-7172-5234)
- David Kutschke (ORCID: https://orcid.org/0009-0002-0154-2357)
- Markus Sperandio (ORCID: https://orcid.org/0000-0002-7689-3613)
- Lin Yang (ORCID: https://orcid.org/0000-0003-0469-9288)
- François Huaux (ORCID: https://orcid.org/0000-0002-4048-7605)
- Riccardo Leinardi (ORCID: https://orcid.org/0000-0002-2570-3568)
- Ali Önder Yildirim (ORCID: https://orcid.org/0000-0003-1969-480X)
- Tobias Stoeger (ORCID: https://orcid.org/0000-0002-2790-0389)
- Chenxi Li (ORCID: https://orcid.org/0000-0001-9766-5751)
- Lianyong Han (ORCID: https://orcid.org/0000-0001-8623-776X)
- Yang Guo
- Juliet Wilmot
Institutions
- Shanghai Jiao Tong University (CN)
- Cancer Research UK (GB)
- German Center for Lung Research (DE)
- Max Planck Institute for Molecular Biomedicine (DE)
- University of Glasgow (GB)
- Ludwig-Maximilians-Universität München (DE)
- UCLouvain (BE)
Publication Details
- Journal
- Science Advances
- Published
- 2025-11-07
- DOI
- https://doi.org/10.1126/sciadv.adx8586
- Citations
- 1
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.80