title: Silica suppresses Toll-like receptor ligand-induced dendritic cell activation.
abstract: 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.
authors.affiliation: Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812-1552, USA. celine.beamer@umontana.edu
authors.forename: Celine A
authors.initials: CA
authors.lastname: Beamer
authors.forename: Andrij
authors.initials: A
authors.lastname: Holian
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D004198:Disease Susceptibility / Q000139:chemically induced; D007239:Infections / Q000139:chemically induced; D007249:Inflammation; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D051117:Scavenger Receptors, Class A; D012822:Silicon Dioxide / Q000009:adverse effects* / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008024:Ligands; D051117:Scavenger Receptors, Class A; D051193:Toll-Like Receptors; D012822:Silicon Dioxide