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Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
β-Glucan-Functionalized Nanoparticles Down-Modulate the Proinflammatory Response of Mononuclear Phagocytes Challenged
Tânia Lima1,2,3, Stefán B Gunnarsson4,5, Elisabete Coelho6
1I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
Abstract:
Systemic fungal infections are associated with significant morbidity and mortality, and Candida albicans is the most common causative agent. Recognition of yeast cells by immune cell surface receptors can trigger phagocytosis of fungal pathogens and a pro-inflammatory response that may contribute to fungal elimination. Nevertheless, the elicited inflammatory response may be deleterious to the host by causing excessive tissue damage. We developed a nanoparticle-based approach to modulate the host deleterious inflammatory consequences of fungal infection by using β1,3-glucan-functionalized polystyrene (β-Glc-PS) nanoparticles. β-Glc-PS nanoparticles decreased the levels of the proinflammatory cytokines TNF-α, IL-6, IL-1β and IL-12p40 detected in in vitro culture supernatants of bone marrow-derived dendritic cells and macrophage challenged with C. albicans cells. Moreover, β-Glc-PS nanoparticles impaired the production of reactive oxygen species by bone marrow-derived dendritic cells incubated with C. albicans. This immunomodulatory effect was dependent on the nanoparticle size. Overall, β-Glc-PS nanoparticles reduced the proinflammatory response elicited by fungal cells in mononuclear phagocytes, setting the basis for a targeted therapy aimed at protecting the host by lowering the inflammatory cost of infection.
Insights
New nanoparticles reduce harmful inflammation caused by Candida albicans fungal infections. This approach uses beta-glucan-functionalized nanoparticles to protect the host from excessive immune responses during infection.
Area of Science:
- Immunology
- Nanotechnology
- Infectious Diseases
Background:
- Systemic fungal infections, particularly those caused by Candida albicans, lead to severe illness and death.
- Immune responses, while crucial for eliminating fungi, can cause harmful inflammation and tissue damage.
Purpose of the Study:
- To develop a nanoparticle-based strategy to mitigate the detrimental inflammatory effects of fungal infections.
- To investigate the immunomodulatory potential of beta-1,3-glucan-functionalized polystyrene (β-Glc-PS) nanoparticles.
Main Methods:
- Utilized β-Glc-PS nanoparticles to treat immune cells (dendritic cells and macrophages) exposed to Candida albicans in vitro.
- Measured levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12p40) and reactive oxygen species production.
- Assessed the impact of nanoparticle size on immunomodulatory effects.
Main Results:
- β-Glc-PS nanoparticles significantly reduced pro-inflammatory cytokine production by immune cells challenged with C. albicans.
- Nanoparticles impaired reactive oxygen species generation in dendritic cells exposed to the fungus.
- The observed immunomodulatory effects were dependent on the size of the nanoparticles.
Conclusions:
- β-Glc-PS nanoparticles effectively dampen the pro-inflammatory response of mononuclear phagocytes to fungal cells.
- This nanoparticle-based approach offers a potential therapeutic strategy to protect hosts by reducing the inflammatory burden of fungal infections.
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