Orally administered CpG oligodeoxynucleotide induces production of CXC and CC chemokines in the gastric mucosa and suppresses bacterial colonization in a mouse model of Helicobacter pylori infection.
Bacterial DNA and unmethylated CpG oligodeoxynucleotides (CpG ODN) are known to be potent stimulators of the innate immune system in vitro and in vivo. We therefore investigated if oral administration of CpG ODN could enhance innate immunity in the gastric mucosa and control the extent of Helicobacter pylori infection in mice. Intragastric administration of a single dose of CpG ODN significantly increased local production of the CC chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES and the CXC chemokine gamma interferon-inducible protein 10 in the stomach and/or the small intestine. Importantly, intragastric administration of CpG ODN to mice with an already established H. pylori infection, in the absence of any coadministered antigen, was found to reduce the bacterial load in the stomach compared to the load in H. pylori-infected control mice, while similar administration of non-CpG ODN had no effect on the bacterial load. The reduction in the bacterial numbers in the stomachs of mice treated with CpG ODN was associated with enhanced infiltration of immune cells and increased RANTES production in the gastric mucosa compared to the infiltration of immune cells and RANTES production in H. pylori-infected control animals. These findings suggest that intragastric administration of CpG ODN without antigen codelivery may represent a valuable strategy for induction of innate immunity against H. pylori infection.
Raghavan
S
S
Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, S 41346 Göteborg, Sweden.
Nyström
J
J
Fredriksson
M
M
Holmgren
J
J
Harandi
A M
AM
D000284:Administration, Oral; D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D018899:CpG Islands; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000254:growth & development; D007113:Immunity, Innate; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology
C408982:CPG-oligonucleotide; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D009838:Oligodeoxyribonucleotides