Silver (Ag) nanoparticles (NPs) are widely used in consumer products potentially exposing humans via lungs, skin, digestive tract and insertion of medical devices. Therefore, biological risk assessments of Ag NPs are critical. We assessed the effect of Ag NPs [colloidal silver spheres of 20 nm (Ag20) and 110 nm diameters (Ag110) stabilized with either citrate or polyvinlypyrrolidone (PVP)] on human innate immune responses to Mycobacterium tuberculosis (M.tb), a respiratory pathogen that causes TB. Human monocyte-derived macrophages (MDMs), a model for alveolar macrophages, were exposed to multiple Ag NP doses for 4 hours. Ag NPs (at nontoxic concentrations, MTS assay) increased the expression of mRNA encoding IL8 (p<0.05) while decreasing the expression of mRNA encoding IL10 (p<0.05). Co-exposure of MDMs to Ag NPs and M.tb suppressed the M.tb-induced expression of mRNAs encoding IL1B, IL10, and TNFA in an Ag NP concentration-dependent manner (p<0.05). Ag20-citrate and Ag20-PVP showed stronger inhibitory activities than Ag110-citrate and Ag110-PVP. Ag NPs suppressed antimycobacterial immune responses by inhibiting NF-κB target genes including CSF2, CSF3, IL6, IL1A, IL1B and TNFA, components of the pathogen-induced TLR signaling pathway, crucial for innate antimycobacterial host immunity. These observations may be explained by the strong induction (p<0.05) of mRNA encoding Hsp72 following Ag NP exposure. Hsp72 can potentially inhibit M.tb-induced NF-κB activation.

2014