title: Different cytokine production and Toll-like receptor expression induced by heat-killed invasive and carrier strains of Neisseria meningitidis.
abstract: Neisseria meningitidis may cause severe invasive disease. The carriage state of the pathogen is common, and the reasons underlying why the infection becomes invasive are not fully understood. The aim of this study was to compare the differences between invasive and carrier strains in the activation of innate immunity. The monocyte expression of TLR2, TLR4, CD14, and HLA-DR, cytokine production, and the granulocyte oxidative burst were analyzed after in vitro stimulation by heat-killed invasive (n = 14) and carrier (n = 9) strains of N. meningitidis. The expression of the cell surface markers in monocytes, the oxidative burst, and cytokine concentrations were measured using flow cytometry. Carrier strains stimulated a higher production of inflammatory cytokines and oxidative burst in granulocytes than invasive strains (all p < 0.001), whereas invasive strains significantly up-regulated TLR2, TLR4 (p < 0.001), and CD14 (p < 0.01) expression on monocytes. Conversely, the monocyte expression of HLA-DR was higher after the stimulation by carrier strains (p < 0.05) in comparison to invasive strains. The LPS inhibitor polymyxin B abolished the differences between the strains. Our findings indicate different immunostimulatory potencies of invasive strains of N. meningitidis compared with carrier strains.
authors.affiliation: Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital, Prague, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Potmesil
authors.forename: Ondrej
authors.initials: O
authors.lastname: Beran
authors.forename: Martin
authors.initials: M
authors.lastname: Musilek
authors.forename: Pavla
authors.initials: P
authors.lastname: Kriz
authors.forename: Michal
authors.initials: M
authors.lastname: Holub
mesh_terms: D002353:Carrier State / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D006684:HLA-DR Antigens / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008589:Meningococcal Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D010587:Phagocytosis; D016897:Respiratory Burst; D013045:Species Specificity; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
keywords: Neisseria meningitidis; cytokines; heat-killed; toll-like receptor 2; toll-like receptor 4