Smaller sizes of Ag-PVP Nanoparticles Control Inflammatory Responses, and Reduce CD80 and CD86 Expression Levels, in Macrophages Infected with Chlamydia trachomatis

摘要

Chlamydia trachomatis is an important cause of sexually transmitted infections that can manifest itself as either acute cervicitis, pelvic inflammatory disease, and more commonly as a chronic asymptomatic infection. One of the most important factors affecting the potential effectiveness of Chlamydia control program is the timing of inflammation. Early intervention strategies that can reduce excessive inflammatory responses could benefit control efforts in reducing the disease severity. Previously we reported that poly-vinyl pyrrolidone (PVP)-coated silver (Ag) nanoparticles (Ag-PVP) at 5-10 nm reduced pro-inflammatory cytokine (IL-6 and TNF) production levels by up to 75% in mouse J774 macrophages infected with C. trachomatis. Here we hypothesize that the anti-inflammatory actions of Ag-PVP maybe dependent on the nanoparticle size. We tested three different sizes of Ag-PVP (10, 20 and 80 nm) for their abilities to reduce pro-inflammatory cytokines in macrophages infected with C. trachomatis. Our results show by cytokine specific ELISAs that all sizes of Ag-PVP reduced IL-6 and TNF as elicited from macrophages infected with live C. trachomatis, with the 10 nm size exhibiting the greatest anti-inflammatory effect. Our MTT assay shows that the anti-inflammatory effect of Ag-PVP is not due to cell death at the concentration used. However, at higher concentrations all tested Ag-PVP sizes were toxic to cells. We also demonstrated by flow cytometry the ability of Ag-PVP (5-10 nm) to reduce the expression levels of CD80 and CD86 co-stimulatory molecules on infected macrophages. This interesting finding suggests their potential to control not only pro-inflammatory cytokines produced by innate immune cells but also those produced by C. trachomatis activated T cells during the adaptive immune response. Overall our data imply that low concentration and smaller size Ag-PVPs are more effective as regulators of the inflammatory response to C. trachomatis and that further investigations can be made using these nanoparticles to combat inflammation induced by this bacterium.