Gold nanoparticles (AuNPs) impair LPS-driven immune responses by promoting a tolerogenic-like dendritic cell phenotype with altered endosomal structures
Michelini, Sara (Paris-Lodron University Salzburg)
Barbero, Francesco (Institut Català de Nanociència i Nanotecnologia)
Prinelli, Alessandra (AvantiCell Science Ltd)
Steiner, Philip (University Salzburg)
Weiss, Richard (Paris-Lodron University Salzburg)
Verwanger, Thomas (Paris-Lodron University Salzburg)
Andosch, Ancuela (Paris-Lodron University Salzburg)
Lütz-Meindl, Ursula (Paris-Lodron University Salzburg)
Puntes, Víctor (Institut Català de Nanociència i Nanotecnologia)
Drobne, Damjana (Univerza V Ljubljani)
Duschl, Albert (Paris-Lodron University Salzburg)
Horejs-Hoeck, Jutta (Paris-Lodron University Salzburg)

Data:	2021
Resum:	Dendritic cells (DCs) shape immune responses by influencing T-cell activation. Thus, they are considered both an interesting model for studying nano-immune interactions and a promising target for nano-based biomedical applications. However, the accentuated ability of nanoparticles (NPs) to interact with biomolecules may have an impact on DC function that poses an unexpected risk of unbalanced immune reactions. Here, we investigated the potential effects of gold nanoparticles (AuNPs) on DC function and the consequences for effector and memory T-cell responses in the presence of the microbial inflammatory stimulus lipopolysaccharide (LPS). Overall, we found that, in the absence of LPS, none of the tested NPs induced a DC response. However, whereas 4-, 8-, and 11 nm AuNPs did not modulate LPS-dependent immune responses, 26 nm AuNPs shifted the phenotype of LPS-activated DCs toward a tolerogenic state, characterized by downregulation of CD86, IL-12 and IL-27, upregulation of ILT3, and induction of class E compartments. Moreover, this DC phenotype was less proficient in promoting Th1 activation and central memory T-cell proliferation. Taken together, these findings support the perception that AuNPs are safe under homeostatic conditions; however, particular care should be taken in patients experiencing a current infection or disorders of the immune system.
Ajuts:	European Commission 671881
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nanoscale, Vol. 13, Issue 16 (April 2021) , p. 7648-7666, ISSN 2040-3372

DOI: 10.1039/d0nr09153g
PMID: 33928963

19 p, 7.4 MB

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