Differential uptake of nanoparticles and microparticles by pulmonary APC subsets induces discrete immunological imprints

Hardy, C, LeMasurier, J, Mohamud, R, Yao, J, Xiang, S, Rolland, J, O'Hehir, R and Plebanski, M 2013, 'Differential uptake of nanoparticles and microparticles by pulmonary APC subsets induces discrete immunological imprints', Journal of Immunology, vol. 191, no. 10, pp. 5278-5290.


Document type: Journal Article
Collection: Journal Articles

Title Differential uptake of nanoparticles and microparticles by pulmonary APC subsets induces discrete immunological imprints
Author(s) Hardy, C
LeMasurier, J
Mohamud, R
Yao, J
Xiang, S
Rolland, J
O'Hehir, R
Plebanski, M
Year 2013
Journal name Journal of Immunology
Volume number 191
Issue number 10
Start page 5278
End page 5290
Total pages 13
Publisher American Association of Immunologists
Abstract There is increasing interest in the use of engineered particles for biomedical applications, although questions exist about their proinflammatory properties and potential adverse health effects. Lung macrophages and dendritic cells (DC) are key regulators of pulmonary immunity, but little is known about their uptake of different sized particles or the nature of the induced immunological imprint. We investigated comparatively the immunological imprints of inert nontoxic polystyrene nanoparticles 50 nm in diameter (PS50G) and 500 nm in diameter (PS500G). Following intratracheal instillation into naive mice, PS50G were preferentially taken up by alveolar and nonalveolar macrophages, B cells, and CD11b+ and CD103+ DC in the lung, but exclusively by DC in the draining lymph node (LN). Negligible particle uptake occurred in the draining LN 2 h postinstillation, indicating that particle translocation does not occur via lymphatic drainage. PS50G but not PS500G significantly increased airway levels of mediators that drive DC migration/maturation and DC costimulatory molecule expression. Both particles decreased frequencies of stimulatory CD11b+MHC class IIhi allergen-laden DC in the draining LN, with PS50G having the more pronounced effect. These distinctive particle imprints differentially modulated induction of acute allergic airway inflammation, with PS50G but not PS500G significantly inhibiting adaptive allergen-specific immunity. Our data show that nanoparticles are taken up preferentially by lung APC stimulate cytokine/chemokine production and pulmonary DC maturation and translocate to the lung-draining LN via cell-associated transport. Collectively, these distinctive particle imprints differentially modulate development of subsequent lung immune responses. These findings support the development of lung-specific particulate vaccines, drug delivery systems, and immunomodulators.
Subject Immunology not elsewhere classified
DOI - identifier 10.4049/jimmunol.1203131
Copyright notice © 2013 by The American Association of Immunologists, Inc.
ISSN 0022-1767
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