Gold Nanoparticles Modulate BCG-Induced Innate Immune Memory in Human Monocytes by Shifting the Memory Response towards Tolerance. 2020

Benjamin J Swartzwelter, and Francesco Barbero, and Alessandro Verde, and Maria Mangini, and Marinella Pirozzi, and Anna Chiara De Luca, and Victor F Puntes, and Luciana C C Leite, and Paola Italiani, and Diana Boraschi
Institute of Biochemistry and Cell Biology, CNR, Via P. Castellino 111, 80131 Napoli, Italy.

Innate immune memory is characterized by a modulation in the magnitude with which innate immune cells such as monocytes and macrophages respond to potential dangers, subsequent to previous exposure to the same or unrelated agents. In this study, we have examined the capacity of gold nanoparticles (AuNP), which are already in use for therapeutic and diagnostic purposes, to modulate the innate memory induced by bacterial agents. The induction of innate memory was achieved in vitro by exposing human primary monocytes to bacterial agents (lipopolysaccharide -LPS-, or live Bacille Calmette-Guérin -BCG) in the absence or presence of AuNP. After the primary activation, cells were allowed to return to a resting condition, and eventually re-challenged with LPS. The induction of memory was assessed by comparing the response to the LPS challenge of unprimed cells with that of cells primed with bacterial agents and AuNP. The response to LPS was measured as the production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). While ineffective in directly inducing innate memory per se, and unable to influence LPS-induced tolerance memory, AuNP significantly affected the memory response of BCG-primed cells, by inhibiting the secondary response in terms of both inflammatory and anti-inflammatory factor production. The reprogramming of BCG-induced memory towards a tolerance type of reactivity may open promising perspectives for the use of AuNP in immunomodulatory approaches to autoimmune and chronic inflammatory diseases.

UI MeSH Term Description Entries
D007108 Immune Tolerance The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D007156 Immunologic Memory The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus. Immune Memory,Immunological Memory,Memory, Immunologic,Immune Memories,Immunologic Memories,Immunological Memories,Memory, Immune,Memory, Immunological
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D006046 Gold A yellow metallic element with the atomic symbol Au, atomic number 79, and atomic weight 197. It is used in jewelry, goldplating of other metals, as currency, and in dental restoration. Many of its clinical applications, such as ANTIRHEUMATIC AGENTS, are in the form of its salts.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001500 BCG Vaccine An active immunizing agent and a viable avirulent attenuated strain of MYCOBACTERIUM BOVIS, which confers immunity to mycobacterial infections. It is used also in immunotherapy of neoplasms due to its stimulation of antibodies and non-specific immunity. Bacillus Calmette Guerin Vaccine,Calmette Guerin Bacillus Vaccine,Calmette's Vaccine,Calmette Vaccine,Calmettes Vaccine,Vaccine, BCG,Vaccine, Calmette's
D053768 Metal Nanoparticles Nanoparticles produced from metals whose uses include biosensors, optics, and catalysts. In biomedical applications the particles frequently involve the noble metals, especially gold and silver. Metal Nanocrystals,Metallic Nanocrystals,Metallic Nanoparticles,Metal Nanocrystal,Metal Nanoparticle,Metallic Nanocrystal,Metallic Nanoparticle,Nanocrystal, Metal,Nanocrystal, Metallic,Nanocrystals, Metal,Nanocrystals, Metallic,Nanoparticle, Metal,Nanoparticle, Metallic,Nanoparticles, Metal,Nanoparticles, Metallic

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