Genomic DNA released by dying cells induces the maturation of APCs.
Mature APCs play a key role in the induction of Ag-specific immunity. This work examines whether genomic DNA released by dying cells provides a stimulus for APC maturation. Double-stranded but not single-stranded genomic DNA triggered APC to up-regulate expression of MHC class I/II and various costimulatory molecules. Functionally, dsDNA enhanced APC function in vitro and improved primary cellular and humoral immune responses in vivo. These effects were dependent on the length and concentration of the dsDNA but were independent of nucleotide sequence. The maturation of APC induced by dsDNA may promote host survival by improving immune surveillance at sites of tissue injury/infection.
Ishii
K J
KJ
Section of Retroviral Immunology, Center for Biologics and Evaluation Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Suzuki
K
K
Coban
C
C
Takeshita
F
F
Itoh
Y
Y
Matoba
H
H
Kohn
L D
LD
Klinman
D M
DM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D053938:DNA Fragmentation; D004269:DNA, Bacterial / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D004269:DNA, Bacterial; D004247:DNA