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 recognize conserved bacterial molecules such as peptidoglycan and lipopolysaccharide. Toll-like receptors (TLR) play a central role in microbe-associated molecular pattern detection. The aim of this study was to compare 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 when compared to low doses. Cytokines were produced in similar dose-dependent profiles regardless of the stimulatory pathogen; however, gram-negative pathogens induced higher cytokine levels when compared to gram-positive bacteria at the same density. These results indicate that gram-positive and gram-negative bacteria differ in their dose-dependent patterns of induction of TLR2 and TLR4, but not cytokine expression.
authors.affiliation: Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University in Prague and University Hospital Bulovka, Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Beran
authors.forename: Roman
authors.initials: R
authors.lastname: Potměšil
authors.forename: Michal
authors.initials: M
authors.lastname: Holub
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis
chemical_list: D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4