TLR2 mediates recognition of live Staphylococcus epidermidis and clearance of bacteremia

Staphylococcus epidermidis (SE) is a nosocomial pathogen that causes catheter-associated bacteremia in the immunocompromised, including those at the extremes of age, motivating study of host clearance mechanisms. SE-derived soluble components engage TLR2; but additional signaling pathways have also...

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Bibliographic Details
Published in:PloS one 2010-04, Vol.5 (4), p.e10111-e10111
Main Authors: Strunk, Tobias, Power Coombs, Melanie R, Currie, Andrew J, Richmond, Peter, Golenbock, Douglas T, Stoler-Barak, Liat, Gallington, Leighanne C, Otto, Michael, Burgner, David, Levy, Ofer
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Apoptosis
Bacteremia
Bacteremia - immunology
Bacteria
Blood
Blood - microbiology
Cells, Cultured
Children & youth
Childrens health
Cytokines
Cytokines - biosynthesis
Francisella tularensis
Health aspects
Hospitals
Immunity, Innate
Immunology/Immunity to Infections
Immunology/Innate Immunity
Immunotherapy
Infection
Infectious diseases
Infectious Diseases/Bacterial Infections
Leukocytes
Macrophages
Macrophages - microbiology
Medical instruments
Medical research
Mice
Mice, Knockout
Microbiology/Immunity to Infections
Microbiology/Innate Immunity
Neutrophils
Nosocomial infection
Nosocomial infections
Recognition
Sepsis
Signal transduction
Signal Transduction - immunology
Signaling
Staphylococcal Infections - immunology
Staphylococcus epidermidis
Staphylococcus epidermidis - immunology
TLR2 protein
Toll-Like Receptor 2 - deficiency
Toll-Like Receptor 2 - immunology
Toll-like receptors
Vaccines
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Summary:Staphylococcus epidermidis (SE) is a nosocomial pathogen that causes catheter-associated bacteremia in the immunocompromised, including those at the extremes of age, motivating study of host clearance mechanisms. SE-derived soluble components engage TLR2; but additional signaling pathways have also been implicated, and TLR2 can play complex, at times detrimental, roles in host defense against other Staphylococcal spp. The role of TLR2 in responses of primary blood leukocytes to live SE and in clearance of SE bacteremia, the most common clinical manifestation of SE infection, is unknown. We studied TLR2-mediated recognition of live clinical SE strain 1457 employing TLR2-transfected cells, neutralizing anti-TLR antibodies and TLR2-deficient mice. TLR2 mediated SE-induced cytokine production in human embryonic kidney cells, human whole blood and murine primary macrophages, in part via recognition of a soluble TLR2 agonist. After i.v. challenge with SE, early (1 h) cytokine/chemokine production and subsequent clearance of bacteremia (24-48 h) were markedly impaired in TLR2-deficient mice. TLR2 mediates recognition of live SE and clearance of SE bacteremia in vivo.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0010111