PMID- 33928963 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20230920 IS - 2040-3372 (Electronic) IS - 2040-3364 (Print) IS - 2040-3364 (Linking) VI - 13 IP - 16 DP - 2021 Apr 30 TI - Gold nanoparticles (AuNPs) impair LPS-driven immune responses by promoting a tolerogenic-like dendritic cell phenotype with altered endosomal structures. PG - 7648-7666 LID - 10.1039/d0nr09153g [doi] AB - 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. FAU - Michelini, Sara AU - Michelini S AUID- ORCID: 0000-0001-9470-3337 AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. FAU - Barbero, Francesco AU - Barbero F AUID- ORCID: 0000-0001-8704-0651 AD - Insitut Catala de Nanosciencia i Nanotecnologia (ICN2), UAB Campus, Bellaterra, Barcelona 08193, Spain. FAU - Prinelli, Alessandra AU - Prinelli A AD - AvantiCell Science Ltd, Gibbsyard Building, Auchincruive, Ayr, KA6 5HW, UK. FAU - Steiner, Philip AU - Steiner P AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. FAU - Weiss, Richard AU - Weiss R AUID- ORCID: 0000-0003-3185-7253 AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. FAU - Verwanger, Thomas AU - Verwanger T AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. FAU - Andosch, Ancuela AU - Andosch A AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. FAU - Lutz-Meindl, Ursula AU - Lutz-Meindl U AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. FAU - Puntes, Victor F AU - Puntes VF AUID- ORCID: 0000-0001-8996-9499 AD - Insitut Catala de Nanosciencia i Nanotecnologia (ICN2), UAB Campus, Bellaterra, Barcelona 08193, Spain. FAU - Drobne, Damjana AU - Drobne D AUID- ORCID: 0000-0002-5970-7460 AD - Biotechnical Faculty, University of Ljubljana, Vecna pot 111, 1000 Ljubljana, Slovenia. FAU - Duschl, Albert AU - Duschl A AUID- ORCID: 0000-0002-7034-9860 AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. FAU - Horejs-Hoeck, Jutta AU - Horejs-Hoeck J AUID- ORCID: 0000-0002-0984-204X AD - Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at. LA - eng PT - Journal Article PL - England TA - Nanoscale JT - Nanoscale JID - 101525249 RN - 0 (Lipopolysaccharides) RN - 7440-57-5 (Gold) SB - IM MH - Dendritic Cells MH - *Gold MH - Humans MH - Lipopolysaccharides MH - *Metal Nanoparticles/toxicity MH - Phenotype PMC - PMC8087175 COIS- There are no conflicts to declare. EDAT- 2021/05/01 06:00 MHDA- 2021/05/15 06:00 PMCR- 2021/04/15 CRDT- 2021/04/30 08:48 PHST- 2021/04/30 08:48 [entrez] PHST- 2021/05/01 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2021/04/15 00:00 [pmc-release] AID - d0nr09153g [pii] AID - 10.1039/d0nr09153g [doi] PST - ppublish SO - Nanoscale. 2021 Apr 30;13(16):7648-7666. doi: 10.1039/d0nr09153g.