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Infection and Immunity, May 2007, p. 2366-2373, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01649-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

CpG Oligodeoxynucleotide Treatment Enhances Innate Resistance and Acquired Immunity to African Trypanosomes{triangledown}

Tajie H. Harris,1 John M. Mansfield,2 and Donna M. Paulnock1*

Department of Medical Microbiology and Immunology, University of Wisconsin—Madison School of Medicine and Public Health,1 Department of Bacteriology, University of Wisconsin—Madison, Madison, Wisconsin 537062

Received 12 October 2006/ Returned for modification 27 December 2006/ Accepted 19 February 2007

Relative resistance to African trypanosomiasis is based on the development of a type I cytokine response, which is partially dependent on innate immune responses generated through MyD88 and Toll-like receptor 9 (TLR9). Therefore, we asked whether enhancement of the immune response by artificial stimulation with CpG oligodeoxynucleotide (ODN), a TLR9 agonist, would result in enhanced protection against trypanosomes. In susceptible BALB/c mice, relative resistance to infection was significantly enhanced by CpG ODN treatment and was associated with decreased parasite burden, increased cytokine production, and elevated parasite-specific B- and T-cell responses. In relatively resistant C57BL/6 mice, survival was not enhanced but early parasitemia levels were reduced 100-fold and the majority of the parasites were nondividing, short stumpy (SS) forms. CpG ODN treatment of lymphocyte-deficient C57BL/6-scid and BALB/cByJ-scid mice also enhanced survival and reduced parasitemia, indicating that innate resistance to trypanosome infection can be enhanced. In C57BL/6-scid and BALB/cByJ-scid mice, the parasites were also predominantly SS forms during the outgrowth of parasitemia. However, the effect of CpG ODN treatment on parasite morphology was not as marked in gamma interferon (IFN-{gamma})-knockout mice, suggesting that downstream effects of IFN-{gamma} production may play a discrete role in parasite cell differentiation. Overall, these studies provide the first evidence that enhancement of resistance to African trypanosomes can be induced in susceptible animals in a TLR9-dependent manner and that CpG ODN treatment may influence the developmental life cycle of the parasites.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, University of Wisconsin—Madison, 1300 University Ave., Madison, WI 53706-1532. Phone: (608) 265-5857. Fax: (608) 265-8596. E-mail: paulnock{at}wisc.edu

{triangledown} Published ahead of print on 5 March 2007.

Editor: J. F. Urban, Jr.

Infection and Immunity, May 2007, p. 2366-2373, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01649-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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