TLR2 mediates recognition of live Staphylococcus epidermidis and clearance of bacteremia.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
TLR2 mediates recognition of live SE and clearance of SE bacteremia in vivo.
Strunk
Tobias
T
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
Power Coombs
Melanie R
MR
Currie
Andrew J
AJ
Richmond
Peter
P
Golenbock
Douglas T
DT
Stoler-Barak
Liat
L
Gallington
Leighanne C
LC
Otto
Michael
M
Burgner
David
D
Levy
Ofer
O
D000818:Animals; D000906:Antibodies; D016470:Bacteremia / Q000276:immunology*; D001769:Blood / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology; D013212:Staphylococcus epidermidis / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology*
D000906:Antibodies; D016207:Cytokines; D051195:Toll-Like Receptor 2
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