PMID- 29872440 OWN - NLM STAT- MEDLINE DCOM- 20190730 LR - 20231112 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Tannic Acid-Modified Silver and Gold Nanoparticles as Novel Stimulators of Dendritic Cells Activation. PG - 1115 LID - 10.3389/fimmu.2018.01115 [doi] LID - 1115 AB - Silver nanoparticles (AgNPs) are promising new antimicrobial agents against a wide range of skin and mucosal pathogens. However, their interaction with the immune system is currently not fully understood. Dendritic cells (DCs) are crucial during development of T cell-specific responses against bacterial and viral pathogens. We have previously shown that tannic acid-modified silver nanoparticles (TA-AgNPs) consist of a promising microbicide against HSV-2. The aim of this study was to compare the ability of TA-AgNPs or TA-AuNPs of similar sizes (TA-Ag/AuNPs) to induce DCs maturation and activation in the presence of HSV-2 antigens when used at non-toxic doses. First, we used JAWS II DC line to test toxicity, ultrastructure as well as activation markers (MHC I and II, CD40, CD80, CD86, PD-L1) and cytokine production in the presence of TA-Ag/AuNPs. Preparations of HSV-2 treated with nanoparticles (TA-Ag/AuNPs-HSV-2) were further used to investigate HSV-2 antigen uptake, activation markers, TLR9 expression, and cytokine production. Additionally, we accessed proliferation and activation of HSV-2-specific T cells by DCs treated with TA-AgNP/AuNPs-HSV-2. We found that both TA-AgNPs and TA-AuNPs were efficiently internalized by DCs and induced activated ultrastructure. Although TA-AgNPs were more toxic than TA-AuNPs in corresponding sizes, they were also more potent stimulators of DCs maturation and TLR9 expression. TA-Ag/AuNPs-HSV-2 helped to overcome inhibition of DCs maturation by live or inactivated virus through up-regulation of MHC II and CD86 and down-regulation of CD80 expression. Down-regulation of CD40 expression in HSV-2-infected DCs was reversed when HSV-2 was treated with TA-NPs sized >30 nm. On the other hand, small-sized TA-AgNPs helped to better internalize HSV-2 antigens. HSV-2 treated with both types of NPs stimulated activation of JAWS II and memory CD8+ T cells, while TA-AgNPs treatment induced IFN-gamma producing CD4+ and CD8+ T cells. Our study shows that TA-AgNPs or TA-AuNPs are good activators of DCs, albeit their final effect upon maturation and activation may be metal and size dependent. We conclude that TA-Ag/AuNPs consist of a novel class of nano-adjuvants, which can help to overcome virus-induced suppression of DCs activation. FAU - Orlowski, Piotr AU - Orlowski P AD - Military Institute of Hygiene and Epidemiology, Warsaw, Poland. FAU - Tomaszewska, Emilia AU - Tomaszewska E AD - Department of Materials Technology and Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland. FAU - Ranoszek-Soliwoda, Katarzyna AU - Ranoszek-Soliwoda K AD - Department of Materials Technology and Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland. FAU - Gniadek, Marianna AU - Gniadek M AD - Faculty of Chemistry, University of Warsaw, Warsaw, Poland. FAU - Labedz, Olga AU - Labedz O AD - Faculty of Chemistry, University of Warsaw, Warsaw, Poland. FAU - Malewski, Tadeusz AU - Malewski T AD - Museum and Institute of Zoology, Polish Academy of Science, Warsaw, Poland. FAU - Nowakowska, Julita AU - Nowakowska J AD - Laboratory of Electron and Confocal Microscopy, Faculty of Biology, University of Warsaw, Warsaw, Poland. FAU - Chodaczek, Grzegorz AU - Chodaczek G AD - Wroclaw Research Centrum EIT+, Wroclaw, Poland. FAU - Celichowski, Grzegorz AU - Celichowski G AD - Department of Materials Technology and Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland. FAU - Grobelny, Jaroslaw AU - Grobelny J AD - Department of Materials Technology and Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland. FAU - Krzyzowska, Malgorzata AU - Krzyzowska M AD - Military Institute of Hygiene and Epidemiology, Warsaw, Poland. AD - Wroclaw Research Centrum EIT+, Wroclaw, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180522 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Tannins) RN - 3M4G523W1G (Silver) RN - 7440-57-5 (Gold) MH - Animals MH - Biomarkers MH - Cell Line MH - Chlorocebus aethiops MH - Cytokines/metabolism MH - Dendritic Cells/*immunology/metabolism/ultrastructure MH - Gene Expression MH - *Gold/chemistry MH - Herpesvirus 2, Human/immunology MH - Immunophenotyping MH - Lymphocyte Activation/genetics/immunology MH - *Metal Nanoparticles/chemistry/ultrastructure MH - Mice MH - *Silver/chemistry MH - T-Lymphocytes/immunology/metabolism MH - *Tannins/chemistry PMC - PMC5972285 OTO - NOTNLM OT - HSV-2 OT - dendritic cells OT - gold nanoparticles OT - silver nanoparticles OT - tannic acid EDAT- 2018/06/07 06:00 MHDA- 2018/06/07 06:01 PMCR- 2018/01/01 CRDT- 2018/06/07 06:00 PHST- 2018/02/11 00:00 [received] PHST- 2018/05/03 00:00 [accepted] PHST- 2018/06/07 06:00 [entrez] PHST- 2018/06/07 06:00 [pubmed] PHST- 2018/06/07 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.01115 [doi] PST - epublish SO - Front Immunol. 2018 May 22;9:1115. doi: 10.3389/fimmu.2018.01115. eCollection 2018.