Trypanosoma cruzi affects nitric oxide production by murine peritoneal macrophages.
Macrophages from mice that are infected with various intracellular pathogens including Leishmania major, Trypanosoma cruzi, and Salmonella typhimurium are stimulated to produce large quantities of nitric oxide (NO). Both viable and heat-treated L. major amastigotes have been shown to be effective co-signals for NO production in vitro. NO produced by macrophages has anti-microbial and immunosuppressive functions in an immune response. We have shown previously that NO plays a complicated role in T. cruzi infections since macrophages are important both in mediating an immune response against the parasite as well as in mediating immunosuppression. In this study we examined how T. cruzi affects NO production by macrophages from C3HeB/FeJ and C57BL/6 mice in vitro. We found that live trypomastigotes neither stimulate nor decrease NO production by interferon (IFN)-gamma-activated macrophages. However, heat-treated or glutaraldehyde-fixed trypomastigotes of T. cruzi significantly decrease NO production by IFN-gamma-activated macrophages and as a result decrease macrophage-mediated trypanocidal and immunosuppressive activity. We have determined that this decrease in NO production by T. cruzi is not due to stimulation of transforming growth factor-beta production and involves tumor necrosis factor-alpha only in C3HeB/FeJ macrophages. This study demonstrates the complexity of the T. cruzi-macrophage interaction as well as confirms previously demonstrated differences between macrophages from 2 strains of mice.
Pakianathan
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Department of Biology, Wake Forest University, Winston-Salem, North Carolina 27109.
Kuhn
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D000818:Animals; D014355:Chagas Disease / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D011994:Recombinant Proteins; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma