CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis.
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.
Zimmermann
S
S
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany.
Egeter
O
O
Hausmann
S
S
Lipford
G B
GB
Röcken
M
M
Wagner
H
H
Heeg
K
K
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018899:CpG Islands; D017931:DNA Primers / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D017931:DNA Primers; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D015847:Interleukin-4