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Infection and Immunity, January 2002, p. 147-152, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.147-152.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

CpG Oligodeoxynucleotides Enhance Host Defense during Murine Tuberculosis

Nicole P. Juffermans,1,2 Jaklien C. Leemans,1 Sandrine Florquin,3 Annelies Verbon,1,2 Arend H. Kolk,4 Peter Speelman,2 Sander J. H. van Deventer,1 and Tom van der Poll1,2*

Laboratory of Experimental Internal Medicine,1 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine, and AIDS,2 Department of Pathology,3 Academic Medical Center, University of Amsterdam, and the Royal Tropical Institute, Amsterdam, The Netherlands4

Received 7 May 2001/ Returned for modification 16 July 2001/ Accepted 27 September 2001

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.

* Corresponding author. Mailing address: Academic Medical Center, Room G2-130, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-5669111. Fax: 31-20-6977192. E-mail: T.vanderPoll{at}amc.uva.nl.

Editor: S. H. E. Kaufmann

Infection and Immunity, January 2002, p. 147-152, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.147-152.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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