8bec29fee6e3f11d6e047375cd6df4d2 IntJouMol_a2022v23n23p14655.pdf ad12c0ea09d1239cc9f2bd40862bc433909f8f8a IntJouMol_a2022v23n23p14655.pdf 651aa4a546dfdd9e30d5218fbf877d6e3a6b365ccea2314429d1c95a442c3ae3 IntJouMol_a2022v23n23p14655.pdf Title: Induction of Innate Memory in Human Monocytes Exposed to Mixtures of Bacterial Agents and Nanoparticles Subject: We assessed whether concomitant exposure of human monocytes to bacterial agents and different engineered nanoparticles can affect the induction of protective innate memory, an immune mechanism that affords better resistance to diverse threatening challenges. Monocytes were exposed in vitro to nanoparticles of different chemical nature, shape and size either alone or admixed with LPS, and cell activation was assessed in terms of production of inflammatory (TNF, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). After return to baseline conditions, cells were re-challenged with LPS and their secondary “memory” response measured. Results show that nanoparticles alone are essentially unable to generate memory, while LPS induced a tolerance memory response (less inflammatory cytokines, equal or increased anti-inflammatory cytokines). LPS-induced tolerance was not significantly affected by the presence of nanoparticles during the memory generation phase, although with substantial donor-to-donor variability. This suggests that, despite the overall lack of significant effects on LPS-induced innate memory, nanoparticles may have donor-specific effects. Thus, future nanosafety assessment and nanotherapeutic strategies will need a personalized approach in order to ensure both the safety and efficacy of nano medical compounds for individual patients. Keywords: innate immunity; innate memory; nanoparticles; bacteria; LPS; monocytes; macrophages Author: Giacomo Della Camera, Tinghao Liu, Wenjie Yang, Yang Li, Victor F. Puntes, Sabrina Gioria, Paola Italiani and Diana Boraschi Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Nov 24 10:14:42 2022 CET ModDate: Thu Nov 24 10:26:40 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2360292 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IBTYZX+VnURWPalladioL Type 1 Custom yes yes no 10 0 RTPZEG+EURM10 Type 1 Builtin yes yes no 15 0 FYMNIR+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 NHVHZW+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 ZEMAOZ+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 46 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 OJYQXC+CMSY10 Type 1 Builtin yes yes no 74 0 AKMDLL+PalatinoLinotype-Bold CID TrueType 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no 249 0 CZOINJ+EURB10 Type 1 Builtin yes yes no 256 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 260 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-04-18 02:27:11 CEST RepresentationInformation: IntJouMol_a2022v23n23p14655.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-04-17 19:17:31 CEST Size: 2360292 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 512 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Nanoparticle Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Primary Response of Human Monocytes to LPS and Nanoparticles Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Memory Response of Human Monocytes to LPS and Nanoparticles Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Nanoparticle Synthesis and Characterisation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Human Monocyte Isolation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Human Monocyte Activation and Induction of Innate Memory Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Cytotoxicity Evaluation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Assessment of Endotoxin Contamination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Evaluation of Cytokine Production Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Info: Title: Induction of Innate Memory in Human Monocytes Exposed to Mixtures of Bacterial Agents and Nanoparticles Author: Giacomo Della Camera, Tinghao Liu, Wenjie Yang, Yang Li, Victor F. Puntes, Sabrina Gioria, Paola Italiani and Diana Boraschi Subject: We assessed whether concomitant exposure of human monocytes to bacterial agents and different engineered nanoparticles can affect the induction of protective innate memory, an immune mechanism that affords better resistance to diverse threatening challenges. Monocytes were exposed in vitro to nanoparticles of different chemical nature, shape and size either alone or admixed with LPS, and cell activation was assessed in terms of production of inflammatory (TNF, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). After return to baseline conditions, cells were re-challenged with LPS and their secondary “memory” response measured. Results show that nanoparticles alone are essentially unable to generate memory, while LPS induced a tolerance memory response (less inflammatory cytokines, equal or increased anti-inflammatory cytokines). LPS-induced tolerance was not significantly affected by the presence of nanoparticles during the memory generation phase, although with substantial donor-to-donor variability. This suggests that, despite the overall lack of significant effects on LPS-induced innate memory, nanoparticles may have donor-specific effects. Thus, future nanosafety assessment and nanotherapeutic strategies will need a personalized approach in order to ensure both the safety and efficacy of nano medical compounds for individual patients. 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