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Published on: May 31, 2018
Microbial products activate monocytic cells through detergent-resistant membrane microdomains
Slava Epelman1, Byron Berenger, Danuta Stack
1Department of Microbiology and Infectious Diseases, University of Calgary, Alberta, Canada.
Summary
Pseudomonas aeruginosa
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Cystic fibrosis patients experience recurrent lung infections.
- Pseudomonas aeruginosa infections involve destructive inflammatory responses.
- Exoenzyme S (ExoS) from P. aeruginosa activates cells via Toll-like receptor (TLR) pathways.
Purpose of the Study:
- Investigate the role of detergent-resistant membrane microdomains (DRM) in ExoS-mediated signaling.
- Understand how ExoS triggers inflammatory responses in cystic fibrosis.
Main Methods:
- Studied ExoS binding to DRM.
- Analyzed ExoS-induced signaling pathways (NF-kappaB, Erk1/2, Src kinases).
- Disrupted DRM using cholesterol extraction and assessed downstream effects.
Main Results:
- ExoS binds directly to DRM and activates Src kinases within them.
- DRM disruption blocked NF-kappaB, Erk1/2 activation, and TNF-alpha production.
- DRM are essential for monocytic cell activation by various TLR and Nod-like receptor agonists.
Conclusions:
- ExoS requires direct binding to DRM for optimal signaling.
- DRM are crucial platforms for inflammatory signaling in response to P. aeruginosa.
- DRM represent potential therapeutic targets for cystic fibrosis lung infections.
