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United States Department of Agriculture

Agricultural Research Service

Title: DNA from Protozoan Parasites Babesia Bovis, Trypanosoma Cruzi, and T.BRUCEIIS Mitogenic for B Lymphocytes and Stimulates Macrophage Expression of Interleukin-12, Tumor Necrosis Factor Alpha, and Nitric Oxide

Authors
item Shoda, Lisl - WASHINGTON STATE UNIVER
item Kegerreis, Kimberley - WASHINGTON STAE UNIVER
item Suarez, Carlos
item Roditti, Isabel - UNIV OF BERN, SWITZERLAND
item Corral, Ricardo - LAB OF VIROLOGY,ARGENTINA
item Bertot, Gustavo - LAB OF VIROLOGY,ARGENTINA
item Norimine, Junzo - WASHINGTON STATE UNIVER
item Brown, Wendy - WASHINGTON STATE UNIVER

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 5, 2001
Publication Date: N/A

Interpretive Summary: Better understanding the immune system mechanisms involved in protection against important protozoan parasites is necessary to design improved preventive methods for disease control. The present study was conducted to determine whether DNA from the protozan parasites B. bovis, Trypanosoma cruzi, and T. brucei activates macrophages to secrete inflammatory mediators associated with protective immunity. The results presented in this study demonstrate that DNA from these three parasites effectively activate cells of the immune system to secrete molecules that are necessary for effective stimulation of the immune system. Thus, recognition of protozoal DNA by immune competent cells may provide an important innate defense mechanism to control parasite replication and promote persistent infection.

Technical Abstract: Activation of macrophages by DNA from protozoan parasites has not been demonstrated. The present study was conducted to determine whether DNA from the protozan parasites B. bovis, Trypanosoma cruzi, and T. brucei activates macrophages to secrete inflammatory mediators associated with protective immunity. DNA from Escherichia coli and all three parasites stimulated B-lymphocyte proliferation and increased macrophage production of interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and nitric oxide (NO). Regulation of IL-12 and NO production occurred at the level of transcription. The amounts of IL-12, TNF-alpha, and NO induced by E. coli and protozoal DNA were strongly correlated (r(2) > 0.9) with the frequency of CG dinucleotides in the genome, and immunostimulation by DNA occurred in the order E. coli >/= T. cruzi > T. brucei > B. bovis. Induction of inflammatory mediators by E. coli, T. brucei, and B. bovis DNA was dependent on the presence of unmethylated CpG dinucleotides. However, at high concentrations, E. coli and T. cruzi DNA-mediated macrophage activation was not inhibited following methylation. These mechanisms may provide an important innate defense mechanism to control parasite replication and promote persistent infection.

Last Modified: 12/18/2014
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