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Publication : CpG oligodeoxynucleotide treatment enhances innate resistance and acquired immunity to African trypanosomes.

First Author  Harris TH Year  2007
Journal  Infect Immun Volume  75
Issue  5 Pages  2366-73
PubMed ID  17339353 Mgi Jnum  J:121887
Mgi Id  MGI:3712597 Doi  10.1128/IAI.01649-06
Citation  Harris TH, et al. (2007) CpG oligodeoxynucleotide treatment enhances innate resistance and acquired immunity to African trypanosomes. Infect Immun 75(5):2366-73
abstractText  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.
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