DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T-brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor alpha, and nitric oxide
Lkm. Shoda et al., DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T-brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor alpha, and nitric oxide, INFEC IMMUN, 69(4), 2001, pp. 2162-2171
The activation of innate immune responses by genomic DNA from bacteria and
several nonvertebrate organisms represents a novel mechanism of pathogen re
cognition. We recently demonstrated the CpG-dependent mitogenic activity of
DNA from the protozoan parasite Babesia bovis for bovine B lymphocytes (W.
C. Brown, D. M. Estes, S. E. Chantler, K. A. Kegerreis, and C. E. Suarez, I
nfect. Immun. 66:5423-5432, 1998). However, activation of macrophages by DN
A from protozoan parasites has not been demonstrated. The present study was
therefore 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 Escher
ichia coli and all three parasites stimulated B-lymphocyte proliferation an
d increased macrophage production of interleukin-12 (IL-12), tumor necrosis
factor alpha (TNF-alpha), and nitric oxide (NO). Regulation of IL-12 and N
O production occurred at the level of transcription. The amounts of IL-12,
TNF-alpha, and NO induced by E. coil and protozoal DNA were strongly correl
ated (r(2) > 0.9) with the frequency of CG dinucleotides in the genome, and
immunostimulation by DNA occurred in the order E. coil greater than or equ
al to 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 un
methylated CpG dinucleotides. However, at high concentrations, E. coli and
T. cruzi DNA-mediated macrophage activation was not inhibited following met
hylation. The recognition of protozoal DNA by B lymphocytes and macrophages
may provide an important innate defense mechanism to control parasite repl
ication and promote persistent infection.