Silica suppresses Toll-like receptor ligand-induced dendritic cell activation.
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
Celine A
CA
Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812-1552, USA. celine.beamer@umontana.edu
Holian
Andrij
A
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*
D016207:Cytokines; D008024:Ligands; D051117:Scavenger Receptors, Class A; D051193:Toll-Like Receptors; D012822:Silicon Dioxide