Trypanosoma cruzi Affects Nitric Oxide Production by Murine Peritoneal Macrophages

Abstract

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.

Induction of phagocytic activity and nitric-oxide production in natural populations of Trypanosoma Cruzi I and II from the state of Paraná, Brazil

“…T. cruzi I parasites and strains isolated from wild reservoirs or triatomines showed the greatest suppression of NO production. These results are in agreement with reports by other authors 36,38 that T. cruzi has developed strategies to evade NO-mediated anti-microbial activity by suppressing its production. The ability of T. cruzi I parasites to escape from NO is in agreement with other biological characteristics of this genetic group, which include its greater infectivity, rate of intracellular replication, and virulence 23,39,47 .…”

“…This difference in behavior may also be a consequence of the isolated behavior of G1 (wild reservoir) and A21A, N914A and N120B (bugs) strains, which displayed significantly higher PI values than the others in the T.cruzi I group. In the case of strain A21A, it was shown that it is a mixture (Tc I+Tc II), in contrast to samples N914A and N120B, which are pure Tc I 36 . In another article from our group (in publication 2 ), using the rRNA gene analysis (24Sα) and mitochondrial DNA (subunit 2 of cytochrome oxidase gene -COII) we found that the G1 strain also belongs to the T. cruzi I group.…”

Canova, a Brazilian medical formulation, alters oxidative metabolism of mice macrophages

“…31 , Toxoplasma gondii 32 and fixed T. cruzi. 33 NO production by macrophages of control group decreased in presence of parasites, suggesting an inhibitory process. However, this decrease was not observed in macrophages from CA treated group.…”

Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensisto nitric oxide correlates with disease severity in Tegumentary Leishmaniasis

“…Alternatively or additionally, NO • -resistant parasite isolates could inhibit NO • production by macrophages, or other killing mechanisms such as ROI. Importantly, it has been shown that M. bovis inhibits NO • -mediated killing by murine macrophages [48], as do Cryptococcus neoformans [49], Trypanosoma cruzi [50], as well, as L. (L.) amazonensis infection [51]. Other studies have reported that amastigote surface enzymes can inhibit NO • production and thereby reduce leishmanicidal activity [52,53].…”