Release of nitric oxide during the experimental infection with Trypanosoma cruzi

Abstract

We analysed the production of nitric oxide (NO) intermediates by cells from BALB/c mice infected with either virulent (Tulahuén or RA) or avirulent (CA-1) strains of Trypanosoma cruzi. Peritoneal or spleen cells from mice infected with T. cruzi released NO when incubated without further stimuli. Cells from mice during the acute stage of infection accumulated higher levels of inducible NO synthase mRNA and produced both, before and after lypopolysaccharide stimulation, higher amounts of NO than cells from mice chronically infected with T. cruzi. NO synthesis showed similar kinetics in connection with all three strains of T. cruzi, but cells from mice inbred with the Tulahuén or RA strains released higher levels of IFN-gamma, an activator of the NO pathways, than cells from mice infected with the CA-1 strain. In vivo administration of L-Ng-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO synthase, increased the susceptibility of mice to T. cruzi. We conclude that infection with T. cruzi induces NO production, and suggest that NO plays a role in the resistance against the parasite.

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

“…In inflammatory conditions, large amounts of • NO can be produced after the induction of inducible NOS (iNOS) in different cell types, notably macrophages. During T. cruzi infection, • NO production, measured by its end products nitrite (NO 2 -) plus nitrate (NO 3 -) (NO x -) in serum or NO 2 -in splenocyte culture supernatants, rises early after the infection and remains high throughout the acute phase (3,4). Most of the current data indicate the necessity for • NO to control the infection.…”

“…It has been proved that mice treated with the • NO inhibitors L-NAME (5) or NGmonomethyl-arginine (NMMA) (3,4) and iNOS knock-out mice (6) are very susceptible to the infection. However, it is important to note that • NO induces immunosuppression by impairing T cell function.…”

“…The animals were infected with a sublethal dose of parasites and treated with the NOS inhibitors L-NAME or GED or with MEG, the latter an iNOS inhibitor and peroxynitrite scavenger (23). L-NAME is a general NOS inhibitor which has already been used to inhibit • NO production during T. cruzi infection (3,4,30). In turn, MEG and GED are guanidino compounds which are more specific for the inhibition of iNOS (31).…”

Intracellular Growth ofTrypanosoma cruziin Cardiac Myocytes Is Inhibited by Cytokine-Induced Nitric Oxide Release

“…The administration of NO inhibitors increases parasitemia and mortality rate in infected mice, further demonstrating the relevant role of NO in the resistance to T. cruzi (16). NO produced by activated macrophages is also known to be cytotoxic for other intracellular pathogens, including Leishmania major, Toxoplasma gondii, Schistosoma mansoni, and Plasmodium falciparum (2,11).…”

Trypanosoma cruzi-Mediated IFN-γ-Inducible Nitric Oxide Output in Macrophages Is Regulated byiNOSmRNA Stability

“…In this context, it seems that some pathogens, including the related parasite Leishmania, down-modulate mouse ⌴ NO generation (9). Understanding how T. cruzi affects NO production in ⌴ is important because these cells are the first to be infected during the onset of murine Chagas' disease (10), are infected before IFN-␥ detection in serum (8), and play a key part in host defense against this parasite (7,8,11,12). Furthermore, NO has been shown to lead to apoptosis (13)(14)(15)(16) and the characteristic suppression of T cell proliferation during acute T. cruzi infections (17)(18)(19).…”