CpG-activated Thy1.2+ dendritic cells protect against lethal Listeria monocytogenes infection.
Synthetic oligodeoxynucleotides containing CpG motifs (CpG ODN) activate the innate immune system by interacting with Toll-like receptor 9. The resultant immune response increases host resistance to infection by a variety of pathogenic microorganisms, including Listeria monocytogenes. There is a considerable interest in harnessing the immunoprotective properties of CpG ODN, yet little is known of the cell phenotype(s) responsible for mediating this protection. This work demonstrates that treatment of mice with CpG ODN increases the number of Thy1.2+, CD11c+ dendritic cells (Thy1.2+ DC) in the spleen, which are both necessary and sufficient for transferring resistance to infection from CpG-treated donors to naive recipients. These CpG-activated Thy1.2+ DC are distinct from conventional (CD11c(hi), Thy1.2-) or plasmacytoid DC (mPDCA+), and secrete IFN-gamma that contributes to protection. These findings suggest that a novel Thy1.2+ DC subset plays a critical role in mediating the immunoprotective activity of CpG DNA.
Ishii
Ken J
KJ
Section of Retroviral Immunology, Center for Biologics Evaluation Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Ito
Shuichi
S
Tamura
Tomohiko
T
Hemmi
Hiroaki
H
Conover
Jacqueline
J
Ozato
Keiko
K
Akira
Shizuo
S
Klinman
Dennis M
DM
D019264:Adoptive Transfer; D000818:Animals; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018800:Thy-1 Antigens / Q000096:biosynthesis*
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D018800:Thy-1 Antigens; D007371:Interferon-gamma