title: Modulation of Human Macrophage Responses to Mycobacterium tuberculosis by Silver Nanoparticles of Different Size and Surface Modification.
abstract: Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications.
authors.affiliation: Department of Environmental and Occupational Health School of Public Health, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Srijata
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Materials and London Center for Nanotechnology, Imperial College, London, United Kingdom.|Department of Mechanical Engineering, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Bey Fen
authors.initials: BF
authors.lastname: Leo
authors.affiliation: Department of Microbiology, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carranza
authors.affiliation: Department of Materials and London Center for Nanotechnology, Imperial College, London, United Kingdom.
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Environmental and Occupational Health School of Public Health, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Cesar
authors.initials: C
authors.lastname: Rivas-Santiago
authors.affiliation: Department of Materials and London Center for Nanotechnology, Imperial College, London, United Kingdom.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Porter
authors.affiliation: Department of Materials and London Center for Nanotechnology, Imperial College, London, United Kingdom.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Ryan
authors.affiliation: Department of Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gow
authors.affiliation: National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.affiliation: Nicholas School of the Environment and Duke Global Health Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Junfeng Jim
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Computational Chemodynamics Laboratory, Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Panos G
authors.initials: PG
authors.lastname: Georgopoulos
authors.affiliation: Department of Biostatistics, Rutgers University School of Public Health, Piscataway, New Jersey, United States of America.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Ohman-Strickland
authors.affiliation: Department of Environmental and Occupational Health School of Public Health, Rutgers University, Piscataway, New Jersey, United States of America.|Center for Global Public Health, School of Public Health, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwander
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002951:Citrates / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects*; D011205:Povidone / Q000494:pharmacology; D061251:Primary Cell Culture; D015398:Signal Transduction; D012834:Silver / Q000633:toxicity*; D000077559:Sodium Citrate
chemical_list: D002951:Citrates; D020099:Coated Materials, Biocompatible; C573415:IFNG protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D016753:Interleukin-10; D000077559:Sodium Citrate; D012834:Silver; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011205:Povidone