Differential immunological effects of silica nanoparticles on peripheral blood mononuclear cells of silicosis patients and controls

Abstract

Silicosis is a fibrotic disease caused by the inhalation of respirable silica particles, which are typically engulfed by alveolar macrophages and subsequently induce the release of inflammatory cytokines. Various animal experimental and human studies have focused on modeling silicosis, to assess the interactions of macrophages and other cell types with silica particles. There is still, however, limited knowledge on the differential response upon silica-exposure between silicosis patients and controls. We focused on studying the responsiveness of peripheral blood mononuclear cells (PBMCs) to silica nanoparticles (SiNPs) - Ludox and NM-200 - of silicosis patients and controls. The proliferative capacity of T- CD3+ and B- CD19+ cells, were evaluated via Carboxyfluorescein succinimidyl ester (CFSE) assay. The activation status of lymphocyte subsets and response to silica were also evaluated by comparing the extent of micro-granuloma or aggregate formation with the cytokine secretion profiles between both groups of individuals. The proliferative capacity of CD19+ cells was elevated in silicotic patients as opposed to controls. Subsets of regulatory T cells (CD4+ CD25+ and CD8+ CD25+) and immunoglobulins IgM and IgG were also significantly increased in patients. The number and the size of aggregates formed were higher with SiNPs stimulation in patients compared to controls. Multivariable analysis also elucidated the role of key cytokines like interleukin-1β (IL-1β), IL-6 and interferon-gamma (IFN-γ), which were upregulated in SiNP-stimulated PBMCs of patients compared to controls. Our ex vivo model thus has potential to provide insights into the immunological effects of silica particles in lymphocytes of silicosis patients and controls.

Analysis of Immune Cell Subsets in Peripheral Blood from Patients with Engineered Stone Silica-Induced Lung Inflammation

“…On the other hand, despite the reduced number of memory B cells in patients with ES-silicosis and the usually low number of circulating plasmablasts in the peripheral blood of healthy controls, we observed a significant increase in plasmablasts in patients with ES-silicosis. Considering plasmablasts as immunoglobulin producers, this may be in line with the increase observed in the levels of immunoglobulins reported in other works [ 10 , 27 , 28 ], although the opposite has also been described [ 13 ]. An important role of certain B lymphocyte subsets in the development of silica-induced lung inflammation and fibrosis has been reported in humans and mice [ 29 , 30 , 31 ].…”

“…Our results revealed a notable increase in the Treg subset in silicosis patients compared with controls. Several studies on silicosis, both in vitro and in animal models, have described an increase in Treg cells [ 27 , 37 , 38 ], and targeted Treg depletion could be used as a therapeutic approach to attenuate the progression of this disease [ 39 ]. On the other hand, a decrease in Tregs has been observed in nonsilicosis CS-exposed workers preceding silicosis development [ 16 ].…”

Silica nanoparticles alleviate the immunosuppression, oxidative stress, biochemical, behavioral, and histopathological alterations induced by Aeromonas veronii infection in African catfish (Clarias gariepinus)

“…It is opined that SiNPs suppress bacterial activity and minimize the dissemination of A. veronii through their promising role in enhancing the immune response. The mechanism of action of SiNPs on innate immunity was recently described by Ganesan et al ( 2022 ), which represented the activating of macrophages and T and B cells and enhancing the release of immunoglobulins. Concurrent with a new report, Abdel Rahman et al ( 2023a ) verified the immunomodulatory role of SiNPs through elevating levels of nitric oxide and immunoglobulin plus up-regulation of the immune-associated genes as interleukins ( IL-8 and IL-1β ) in C. gariepinus .…”

Macrophages reprogramming improves immunotherapy of IL-33 in peritoneal metastasis of gastric cancer

“…FITC-CFSE labeling of SNU601 cells was performed in a 1:1 ratio with a final concentration of CFSE at 2.5 µg/mL, allowed to incubate at room temperature for 8 min while protected from light (Ganesan et al, 2022 ). SNU601 cells were co-cultured with PBMCs for 12 h after stimulating PBMCs with or without human recombinant IL-33 (50 ng/mL) for 48 h. The cell suspension was incubated in the dark for 15 min after adding propidium iodide with a final concentration of 0.5 µg/mL.…”