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Silica suppresses Toll-like receptor ligand-induced dendritic cell activation

Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana, USA

¹Correspondence: Center for Environmental Health Sciences, School of Pharmacy and Allied Health Sciences, 32 Campus Dr., Skaggs Bldg., Rm. 285A, University of Montana, Missoula, MT 59812-1552, USA. E-mail: celine.beamer{at}umontana.edu

Inhalation of silica, without evidence of silicosis, is believed to predispose individuals to bacterial infections and impair respiratory immune functions. Silica may alter the sensitivity of antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs), to other types of infection; however, the exact nature of these exchanges remains uncertain. The purpose of the present study is to characterize the effect of silica exposure on innate pulmonary defense mechanisms following Toll-like receptor (TLR) ligand-induced activation using DCs as a model APC and determine whether these signals act in synergy or opposition to one another. Using C57Bl/6 mice, pattern recognition receptor expression on DCs was examined in vitro and in vivo using flow cytometry, and the activation state of pulmonary and granulocyte-macrophage colony-stimulating factor-derived DCs was assessed in response to silica in combination with TLR ligands (lipopolysaccharide, cytosine-phosphate-guanine, or polyinosinic:polycytidylic acid) using flow cytometry and measurement of cytokine production. In this study, silica attenuated TLR ligand-dependent DC activation with regards to accessory molecule expression as well as nitric oxide and inflammatory cytokine production. Furthermore, silica’s ability to modulate TLR ligand-dependent DC activation did not appear to be dependent on the class A scavenger receptors. Taken together, silica’s ability to alter susceptibility to infection may be due to impaired inflammatory responses and reduced antibacterial activity.—Beamer, C. A., Holian, A. Silica suppresses Toll-like receptor ligand-induced dendritic cell activation.

Key Words: pattern recognition receptor • costimulatory molecule • TLR4 • MARCO