Method of bacterial killing differentially affects the human innate immune response to Staphylococcus epidermidis.
BACKGROUND
In vitro investigations of human innate immune responses to extracellular bacteria commonly utilise killed preparations in preference to live organisms. The effects of the bacterial preparation method on the activation of innate signalling pathways by the common opportunistic pathogen Staphylococcus epidermidis (SE) are unknown.


METHODS
Mononuclear cell cytokine expression patterns induced by live (LSE), heat-killed (HKSE) and ethanol-killed SE (EKSE) were characterized at the transcriptional and translational level. Toll-like receptor (TLR)-activating capacity of the preparations was analysed using TLR-transfected human embryonic kidney cells.


RESULTS
Live SE activated NF-κB, STAT1, type I interferon, and inflammasome pathways. Killed preparations engaged the NF-κB pathway, but had significantly lower capacity to activate other innate immune pathways.


CONCLUSIONS
Killing of extracellular bacteria has significant qualitative and quantitative effects on key aspects of innate responses in vitro. Interpretation of in vitro data and extrapolation of findings should take into account the potential effects of bacterial preparation and should not assume that responses to killed bacteria are predictive of responses to live organisms.
Strunk
Tobias
T
School of Paediatrics and Child Health, University of Western Australia, Subiaco. tobiasstrunk@yahoo.de
Richmond
Peter
P
Prosser
Amy
A
Simmer
Karen
K
Levy
Ofer
O
Burgner
David
D
Currie
Andrew
A
D001433:Bacteriolysis / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D000431:Ethanol / Q000494:pharmacology; D054884:Host-Pathogen Interactions; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000276:immunology*; D051193:Toll-Like Receptors; D015533:Transcriptional Activation; D014162:Transfection
D058847:Inflammasomes; D007370:Interferon Type I; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D051193:Toll-Like Receptors; D000431:Ethanol