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Molecules from Staphylococcus aureus that bind CD14 and stimulate innate immune responses
T Kusunoki1, E Hailman, T S Juan
1Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York 10021, USA.
The Journal of Experimental Medicine
|December 1, 1995
Summary
Researchers discovered a novel component in Staphylococcus aureus that triggers inflammatory responses by binding to CD14, similar to how gram-negative bacteria do. This finding suggests CD14 plays a key role in innate immunity against both types of bacteria.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Mammals initiate rapid inflammatory responses to Gram-negative bacteria via lipopolysaccharide (LPS) binding to CD14.
- This LPS-CD14 interaction triggers cytokine synthesis and adhesion molecule upregulation.
- The specific molecules responsible for innate immune responses to Gram-positive bacteria remain largely undefined.
Purpose of the Study:
- To identify the component in Staphylococcus aureus responsible for initiating innate immune responses.
- To investigate the role of CD14 in mediating responses to Gram-positive bacterial components.
- To characterize the mechanism of action and distinguish the active factor from known bacterial molecules like lipoteichoic acid (LTA).
Main Methods:
- Extraction and fractionation of protein-free components from Staphylococcus aureus.
- Assessing cellular responses (neutrophil adhesion, cytokine production) in monocytes and U373 cells.
- Utilizing CD14 blocking and soluble CD14 addition to evaluate CD14 dependence.
- Investigating the binding interaction between the S. aureus component and CD14, including competition with LPS.
- Testing the effect of LPS binding protein (LBP) and bactericidal/permeability increasing protein (BPI).
- Comparing the activity and properties of the active factor with lipoteichoic acid (LTA).
Main Results:
- A minor component in S. aureus extracts stimulates neutrophil adhesion and cytokine production.
- CD14 is crucial for mediating these responses, with soluble CD14 enhancing sensitivity and blocking CD14 reducing it significantly.
- The S. aureus component binds to CD14 and inhibits LPS binding.
- Unlike LPS, this component's activity is not modulated by LBP or BPI.
- The active factor is distinct from LTA, as shown by differential fractionation, lack of stimulation by pure LTA, and LTA's antagonistic effect on LPS-induced IL-6 production.
Conclusions:
- Mammals likely utilize CD14 for innate immune recognition of both Gram-negative and Gram-positive bacteria.
- Gram-positive bacteria possess a unique, CD14-binding molecule that initiates cellular inflammatory responses.
- This newly identified factor represents a distinct pathway in innate immunity compared to LPS recognition.