Plasmid DNA induces increased lymphocyte trafficking: a specific role for CpG motifs.
Bacterial DNA, primarily through immunostimulatory cytosine-guanine (CpG) motifs, induces the secretion of cytokines and activates a variety of effector cells. We investigated the possibility that CpG motifs might also modulate immunosurveillance by altering cell trafficking through a regional lymph node. Intradermal injection of plasmid DNA induced rapid and prolonged increases in the number of lymphocytes collected in efferent lymph. This effect on cell trafficking was not dependent on the expression of an encoded reporter gene but varied with plasmid construct and required a circular form. Injection of synthetic oligodeoxyribonucleotides containing CpG motifs did not alter lymphocyte trafficking but CpG-enhanced plasmid induced a dose-dependent increase in cell trafficking. Phenotypic analyses revealed that the increase in cell trafficking involved all lymphocyte subpopulations and represented a mass movement of cells. These observations reveal that bacterial DNA, through immunostimulatory CpG motifs, alters immunosurveillance by increasing cell recruitment to a regional lymph node.
Uwiera
R R
RR
Department of Veterinary Pathology, Veterinary Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada.
Gerdts
V
V
Pontarollo
R A
RA
Babiuk
L A
LA
Middleton
D M
DM
Griebel
P J
PJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D018899:CpG Islands; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D004270:DNA, Circular / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D007157:Immunologic Surveillance / Q000276:immunology*; D016130:Immunophenotyping; D007271:Injections, Intradermal; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology; D010957:Plasmids / Q000235:genetics / Q000276:immunology*; D012756:Sheep
D000276:Adjuvants, Immunologic; D004269:DNA, Bacterial; D004270:DNA, Circular; D009838:Oligodeoxyribonucleotides