title: Differences in Toll-like receptor expression and cytokine production after stimulation with heat-killed Gram-positive and Gram-negative bacteria.
abstract: Innate immune surveillance in the blood is executed mostly by circulating monocytes, which recognise conserved bacterial molecules such as peptidoglycan and lipopolysaccharide. Toll-like receptors (TLR) play a central role in microbe-associated molecular pattern detection. Here, we compared the differences in TLR expression and cytokine production after stimulation of peripheral blood cells with heat-killed Gram-negative and Gram-positive human pathogens Neisseria meningitidis, Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae. We found that TLR2 expression is up-regulated on monocytes after stimulation with S. aureus, S. pneumoniae, E. coli and N. meningitidis. Moreover, TLR2 up-regulation was positively associated with increasing concentrations of Gram-positive bacteria, whereas higher concentrations of Gram-negative bacteria, especially E. coli, caused a milder TLR2 expression increase compared with low doses. Cytokines were produced in similar dose-dependent profiles regardless of the stimulatory pathogen; however, Gram-negative pathogens induced higher cytokine levels than Gram-positive ones at same concentrations. These results indicate that Gram-positive and Gram-negative bacteria differ in their dose-dependent patterns of induction of TLR2 and TLR4, but not in cytokine expression.
authors.affiliation: Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University in Prague and University Hospital Bulovka, 180 81, Praha 8, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Beran
authors.forename: R
authors.initials: R
authors.lastname: Potměšil
authors.forename: M
authors.initials: M
authors.lastname: Holub
mesh_terms: D016207:Cytokines / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006090:Gram-Negative Bacteria / Q000235:genetics / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D009000:Monocytes / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4