CpG oligodeoxynucleotides enhance host defense during murine tuberculosis.
Oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs activate immune cells to produce cytokines. CpG ODNs protect mice against infections with intracellular bacteria by the induction of a T helper 1 (Th1) response. To determine the effect of CpG ODNs in pulmonary tuberculosis, mice were treated with CpG ODNs or control ODNs at the time of intranasal infection. CpG ODNs reduced mycobacterial outgrowth for up to 5 weeks after Mycobacterium tuberculosis infection and were associated with a decrease in inflammation in lung tissue. CpG treatment was also associated with elevated levels of gamma interferon (IFN-gamma) and decreased levels of interleukin 4 in the lungs and an increased capacity of splenocytes to secrete Th1-type cytokines. CpG ODNs given 2 weeks after infection were still able to reduce mycobacterial outgrowth and to enhance a Th1 response 5 weeks postinfection. Administration of CpG ODNs to IFN-gamma-gene-deficient mice failed to reduce mycobacterial outgrowth. These data suggest that CpG ODNs improve host defense during pulmonary tuberculosis by an IFN-gamma-dependent mechanism.
Juffermans
Nicole P
NP
Laboratory of Experimental Internal Medicine, Department of Internal Medicine, University of Amsterdam, The Netherlands.
Leemans
Jaklien C
JC
Florquin
Sandrine
S
Verbon
Annelies
A
Kolk
Arend H
AH
Speelman
Peter
P
van Deventer
Sander J H
SJ
van der Poll
Tom
T
D000276:Adjuvants, Immunologic; D000818:Animals; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000517:prevention & control
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma