CD14 plays no major role in shock induced by Staphylococcus aureus but down-regulates TNF-alpha production.
Recent in vitro studies have suggested that CD14, a major receptor for LPS, may also be a receptor for cell wall components of Gram-positive bacteria and thus play a role in Gram-positive shock. To analyze the in vivo role of CD14 in responses to Gram-positive bacteria, CD14-deficient and control mice were injected with Staphylococcus aureus, and the effects on lethality, bacterial clearance, and production of cytokines were analyzed. Survival of CD14-deficient and control mice did not differ significantly after administration of various doses of either unencapsulated or encapsulated S. aureus; furthermore, mice in both groups displayed similar symptoms of shock. In addition, inflammatory cytokines such as TNF-alpha and IL-6 were readily detectable in the serum of CD14-deficient mice injected with live or antibiotic-killed S. aureus. Surprisingly, the serum concentration of TNF-alpha in CD14-deficient mice was at least threefold higher than in control mice after injection of either unencapsulated or encapsulated S. aureus, suggesting that CD14 down-regulates TNF-alpha. A similar increase in serum TNF-alpha occurred when CD14-deficient animals were injected with gentamicin-killed bacteria even though no symptoms of shock were observed. These studies indicate that CD14, in contrast to its key function in responses to the Gram-negative bacterium, Escherichia coli 0111, does not play a prominent role in septic shock induced by S. aureus, and that the symptoms of S. aureus shock are not due solely to TNF-alpha.
Haziot
A
A
North Shore University Hospital/New York University School of Medicine, Manhasset 11030, USA.
Hijiya
N
N
Schultz
K
K
Zhang
F
F
Gangloff
S C
SC
Goyert
S M
SM
D000818:Animals; D016667:Bacterial Capsules / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology*; D005839:Gentamicins / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012772:Shock, Septic / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D016207:Cytokines; D005839:Gentamicins; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha