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.
Highlights
Increased use of nanoparticles (NP) as additives in consumer products may cause frequent human exposures to NP
We examined the effects of AgNP with different sizes and surface modifications on innate immune responses of human monocyte-derived macrophages (MDM) to infection with Mycobacterium tuberculosis (M.tb)
IL1B mRNA expression was shown to be suppressed by AgNP (Fig 9A) while AgNP induced the expression of HSPA1 mRNA which encodes for Hsp72 (Fig 11B)
Summary
Increased use of nanoparticles (NP) as additives in consumer products may cause frequent human exposures to NP. The innate immune system is critical in sensing exposure to NP and functions as a first line of defense against infectious pathogens, only a few studies have assessed the interactions of NP with the human immune system [7,8,9]. Because of their antibacterial properties [10], silver (Ag) NP (AgNP) are among the most widely used NP in consumer products such as textiles, disinfectant sprays, antibacterial ointments, bandages and medical devices such as orthopedic implants. AgNP that are stabilized with weak capping agents such as citrate, which is weakly bound to the Ag core and stabilizes by charge repulsion, tend to aggregate more than those stabilized with strong capping agents such as PVP, which is strongly bound to the Ag core and sterically stabilizes AgNP [15,16,17]
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