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Staphylococcus aureus and derived exotoxins induce nuclear factor kappa B-like activity in murine bone marrow
K Busam1, C Gieringer, M Freudenberg
1Institute of Biochemistry, University of Freiburg, Germany.
Abstract:
Heat-killed gram-positive Staphylococcus aureus as well as S. aureus-derived exotoxins B and toxic shock syndrome toxin 1 can induce nuclear factor kappa B (NF-kappa B)-like activity in murine bone marrow macrophages. The induction of NF-kappa B-like activity in murine macrophages by S. aureus was as effective as induction by tumor necrosis factor alpha (TNF-alpha) or lipopolysaccharides (LPS) and was observed in macrophages derived from LPS-sensitive and LPS-resistant mice. Stimulation of macrophages with S. aureus but not with the exotoxins resulted in the accumulation of TNF-alpha in the culture medium. The induction of NF-kappa B-like activity by S. aureus, however, clearly preceded TNF-alpha secretion and was not inhibited by a neutralizing serum against TNF-alpha. In addition, pretreatment of macrophages with the protein synthesis inhibitor cycloheximide or dexamethasone, which prevented the secretion of TNF-alpha from macrophages, did not interfere with the induction of NF-kappa B-like activity by S. aureus. This findings reveal the existence of bacterial components other than LPS which can induce NF-kappa B-like activity in susceptible cells.
Insights
Staphylococcus aureus components, excluding known toxins, activate nuclear factor kappa B (NF-kappa B)-like pathways in macrophages. This activation occurs independently of tumor necrosis factor alpha (TNF-alpha) secretion.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Staphylococcus aureus (S. aureus) is a significant pathogen.
- Lipopolysaccharides (LPS) are known inducers of inflammatory responses.
- Nuclear factor kappa B (NF-kappa B) is a key transcription factor in immunity.
Purpose of the Study:
- To investigate the ability of S. aureus components to induce NF-kappa B-like activity in macrophages.
- To determine if S. aureus-derived exotoxins induce NF-kappa B-like activity.
- To elucidate the relationship between S. aureus-induced NF-kappa B activation and TNF-alpha secretion.
Main Methods:
- Murine bone marrow macrophages were treated with heat-killed S. aureus, S. aureus exotoxins (Exotoxin B, Toxic Shock Syndrome Toxin 1), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharides (LPS).
- NF-kappa B-like activity was assessed.
- TNF-alpha accumulation in culture medium was measured.
- Macrophage pretreatment with cycloheximide or dexamethasone was performed.
- Neutralizing serum against TNF-alpha was used.
Main Results:
- Heat-killed S. aureus and its exotoxins induced NF-kappa B-like activity in macrophages.
- S. aureus induction of NF-kappa B-like activity was comparable to TNF-alpha and LPS.
- S. aureus, but not its exotoxins, stimulated TNF-alpha secretion.
- NF-kappa B-like activity induction by S. aureus preceded TNF-alpha secretion and was TNF-alpha-independent.
- Inhibition of protein synthesis or TNF-alpha secretion did not affect S. aureus-induced NF-kappa B activation.
Conclusions:
- Bacterial components in S. aureus, distinct from LPS and known exotoxins, can activate NF-kappa B-like pathways in macrophages.
- This activation pathway is independent of TNF-alpha secretion.
- Findings suggest novel mechanisms of S. aureus-mediated immune activation.