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CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis
S Zimmermann1, O Egeter, S Hausmann
1Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany.
Abstract:
Synthetic oligodeoxynucleotides containing CpG dinucleotides (CpG-ODN) mimic the immunostimulatory qualities of bacterial DNA. We asked whether immunostimulation by CpG-ODN predisposes for a commitment toward a Th1 vs a Th2 response in Leishmania major infection, a model for a lethal Th2-driven disease, in BALB/c mice. CpG-ODN induced Th1 effector T cells in vitro and conveyed protective immunity to disease-prone BALB/c mice in vivo. Conversion to a Th1-driven resistant phenotype was associated with IL-12 production and maintained the expression of IL-12R beta2-chains. Most strikingly, CpG-ODN were even curative when given as late as 20 days after lethal L. major infection, indicating that CpG-ODN revert an established Th2 response. These findings imply an important role of bacterial DNA and CpG-ODN in the instruction of adaptive immune responses. They also point to the therapeutic potential of CpG-ODN in redirecting curative Th1 responses in Th2-driven disorders.
Insights
Synthetic DNA (CpG-ODN) shifts immune responses toward Th1, offering protection against Leishmania major infection and even reversing established Th2 responses in mice.
Area of Science:
- Immunology
- Microbiology
Background:
- CpG dinucleotides (CpG-ODN) in bacterial DNA stimulate immune responses.
- Leishmania major infection in BALB/c mice serves as a model for Th2-driven diseases.
Purpose of the Study:
- To investigate if CpG-ODN promotes a Th1 vs. Th2 response in Leishmania major infection.
- To evaluate the therapeutic potential of CpG-ODN in a Th2-driven disease model.
Main Methods:
- In vitro induction of Th1 effector T cells using CpG-ODN.
- In vivo administration of CpG-ODN to BALB/c mice infected with Leishmania major.
- Assessment of immune response phenotype, IL-12 production, and IL-12R beta2-chain expression.
Main Results:
- CpG-ODN induced Th1 effector T cells and conferred protective immunity in disease-prone mice.
- Th1-driven resistance was linked to IL-12 production and sustained IL-12R beta2-chain expression.
- CpG-ODN treatment was curative even when initiated 20 days post-infection, reversing established Th2 responses.
Conclusions:
- CpG-ODN plays a crucial role in directing adaptive immune responses.
- Bacterial DNA, through CpG-ODN, can instruct immune polarization.
- CpG-ODN holds therapeutic promise for redirecting Th1 responses in Th2-driven disorders.