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Keratinocytes determine Th1 immunity during early experimental leishmaniasis
Jan M Ehrchen1, Kirsten Roebrock, Dirk Foell
1Institute of Immunology, University of Muenster, Muenster, Germany.
Plos Pathogens
|May 6, 2010
Summary
Skin
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Experimental leishmaniasis models Th1/Th2 cell differentiation.
- Th1 response confers resistance; Th2 response leads to susceptibility.
- Early tissue microenvironment influences Th-cell differentiation.
Purpose of the Study:
- Analyze differential gene expression in infected skin.
- Identify early triggers for Th-cell differentiation.
- Investigate the role of epidermal cytokines in leishmaniasis outcome.
Main Methods:
- Microarray analysis of infected mouse skin.
- Bioinformatics and in situ hybridization.
- Laser-microdissection of epidermal cells.
Main Results:
- Epidermis is a key source of immunomodulatory mediators.
- Resistant mice showed stronger epidermal gene induction (IL-12, IL-1beta, IL-4, IL-6).
- Epidermal IL-6 upregulation was higher in resistant mice; IL-4 neutralization induced Th2 switch.
Conclusions:
- Epidermal cytokine expression is crucial for protective Th1 immunity.
- Early epidermal cytokine profiles dictate leishmaniasis infection outcome.
- This study reveals a novel mechanism in host-pathogen interaction.
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