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Membrane rafts in host-pathogen interactions
Joachim Riethmüller1, Andrea Riehle, Heike Grassmé
1Children's Hospital, University of Tuebingen, Hoppe-Seyler Str. 1, 72076 Tuebingen, Germany.
Abstract:
Central elements in the infection of mammalian cells with viral, bacterial and parasitic pathogens include the adhesion of the pathogen to surface receptors of the cell, recruitment of additional receptor proteins to the infection-site, a re-organization of the membrane and, in particular, the intracellular signalosome. Internalization of the pathogen results in the formation of a phagosome that is supposed to fuse with lysosomes to form phagolysosomes, which serve the degradation of the pathogen, an event actively prevented by some pathogens. In summary, these changes in the infected cell permit pathogens to trigger apoptosis (for instance of macrophages paralysing the initial immune response), to invade the cell and/or to survive in the cell, but they also serve the mammalian cell to defeat the infection, for instance by activation of transcription factors and the release of cytokines. Distinct membrane domains in the plasma membrane and intracellular vesicles that are mainly composed of sphingolipids and cholesterol or enriched with the sphingolipid ceramide, are critically involved in all of these events occurring during the infection. These membrane structures are therefore very attractive targets for novel drugs to interfere with bacterial, viral and parasitic infections.
Insights
Pathogens infect mammalian cells by altering cell membranes and intracellular signaling. Targeting specific membrane domains offers a novel strategy to combat viral, bacterial, and parasitic infections.
Area of Science:
- Cellular biology
- Pathogen-host interactions
- Membrane biophysics
Background:
- Pathogen infection involves cell surface adhesion, receptor recruitment, membrane reorganization, and intracellular signalosome modulation.
- Pathogen internalization leads to phagosome formation, with fusion to lysosomes for degradation, an event pathogens may actively inhibit.
- Infected cells undergo changes to facilitate pathogen invasion, survival, or trigger host immune responses like apoptosis and cytokine release.
Purpose of the Study:
- To elucidate the role of distinct membrane domains in host-pathogen interactions.
- To identify potential therapeutic targets for anti-infective drug development.
Main Methods:
- Analysis of pathogen adhesion mechanisms.
- Investigation of host cell membrane dynamics during infection.
- Characterization of intracellular signaling pathways involved in infection.
- Examination of membrane domain composition (sphingolipids, cholesterol, ceramide).
Main Results:
- Specific membrane domains, rich in sphingolipids, cholesterol, or ceramide, are crucial for pathogen adhesion, internalization, and intracellular survival.
- Pathogens manipulate host cell membranes and signaling pathways to promote infection.
- Host cells utilize these membrane domains to initiate immune responses.
Conclusions:
- Distinct membrane domains are critical sites for pathogen manipulation and host defense during infection.
- Targeting these specific membrane structures presents a promising strategy for developing new anti-infective therapies against a range of pathogens.
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