Role of nitric oxide in resistance and histopathology during experimental infection with Trypanosoma cruzi

Petray, Patricia; Castaños‐Vélez, Esmeralda; Grinstein, S; Örn, Anders; Rottenberg, Martı́n E.

doi:10.1016/0165-2478(95)00083-h

Cited by 77 publications

(63 citation statements)

References 28 publications

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“…30 In the myocardium, immunostaining has showed a predominance of CD8 ϩ T lymphocytes with few CD4 ϩ lymphocytes and macrophages. 31 Moreover, there is evidence for the participation of activated macrophages in the control of T. cruzi infection through the production of nitric oxide, [32][33][34] as occurs in infections with other intracellular parasites. The expression of tumor necrosis factor-␣, interleukin-1␤, and the inducible nitric oxide synthase (NOS2) is increased in the heart of infected mice.…”

Section: Discussionmentioning

confidence: 99%

Infection with different Trypanosoma cruzi populations in rats: myocarditis, cardiac sympathetic denervation, and involvement of digestive organs.

Camargos¹,

Franco²,

Garcia³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. We tested four isolates of Trypanosoma cruzi to assess parasite virulence and ability to cause myocarditis, cardiac sympathetic denervation, and histopathologic alterations in organs of the digestive system. The susceptibility of rats depends on the population of T. cruzi, with the ABC strain and the CL-Brener clone killing all animals, regardless of the parasitemic pattern. All tested T. cruzi populations caused acute myocarditis, but failed to induce histologic alterations in the intestine. The Cl-Brener and ABC isolates caused esophageal myositis. The myocarditis caused by the ABC, CL-Brener, and Y isolates was severe, but resolution started at the end of the acute phase. In contrast, the Col 1.7G2 clone induced mild and sustained myocarditis. Our results also showed that T. cruzi populations able to induce severe acute myocarditis caused marked sympathetic denervation, but recovery of normal cardiac histology and innervation occurred. The sustained myocarditis induced by Col 1.7 G2 clone failed to cause sustained denervation.

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Section: Discussionmentioning

confidence: 99%

Infection with different Trypanosoma cruzi populations in rats: myocarditis, cardiac sympathetic denervation, and involvement of digestive organs.

Camargos¹,

Franco²,

Garcia³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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“…Mice received a daily intraperitoneal dose of 50 mg/kg L-NAME, 10 mg/kg MEG or 7 mg/kg GED diluted in PBS or vehicle from the day of infection and throughout the experimental period. Similar L-NAME doses have been shown to inhibit • NO production during T. cruzi infection in mice (3,5). Also, 10 mg/kg MEG inhibited • NO formation and nitrotyrosine immunoreactivity in a rat model of lung inflammation (24).…”

Section: Pharmacological Interventionmentioning

confidence: 99%

“…Most of the current data indicate the necessity for • NO to control the infection. The production of • NO correlates with the resistance to T. cruzi infection in C57BL/6 mice (3), and the use of different iNOS inhibitors dramatically increases parasitemia and mortality (5). Indeed, interferon-γ (INF-γ) receptor or iNOS knock-out mice are extremely susceptible to T. cruzi infection (6)(7)(8).…”

Section: • • •mentioning

confidence: 99%

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Naviliat

Gualco

Cayota

et al. 2005

Braz J Med Biol Res

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Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO 2 ) group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of • NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of • NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G -nitroarginine methyl ester treatment abolished • NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanidoethyl disulfide, at doses that moderately reduced the • NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce • NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

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“…To evaluate the relevance of MDSCs, we followed an alternative approach: we inhibited iNOS with L-NAME treatment of infected mice resulting in a dramatic increase in parasitemia, mortality, and parasite load in heart tissue with respect to untreated mice, showing that iNOS, and by extension NO-producing MDSCs, are necessary to control the T. cruzi infection (31)(32)(33)(34). In addition, Larginine supplementation reduced parasite burden in heart tissue, indicating that restoration of L-arginine levels is beneficial for the host.…”

Section: Ly6gmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells Infiltrate the Heart in Acute Trypanosoma cruzi Infection

Cuervo

Guerrero

Carbajosa

et al. 2011

The Journal of Immunology

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Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects several million people in Latin America. Myocarditis, observed in the acute and chronic phases of the disease, is characterized by a mononuclear cell inflammatory infiltrate. We previously identified a myeloid cell population in the inflammatory heart infiltrate of infected mice that expressed arginase I. In this study, we purified CD11b+ myeloid cells from the heart and analyzed their phenotype and function. Those CD11b+ cells were ∼70% Ly6G−Ly6C+ and 25% Ly6G+Ly6C+. Moreover, purified CD11b+Ly6G− cells, but not Ly6G+ cells, showed a predominant monocytic phenotype, expressed arginase I and inducible NO synthase, and suppressed anti-CD3/anti-CD28 Ab-induced T cell proliferation in vitro by an NO-dependent mechanism, activity that best defines myeloid-derived suppressor cells (MDSCs). Contrarily, CD11b+Ly6G+ cells, but not CD11b+Ly6G− cells, expressed S100A8 and S100A9, proteins known to promote recruitment and differentiation of MDSCs. Together, our results suggest that inducible NO synthase/arginase I-expressing CD11b+Ly6G− myeloid cells in the hearts of T. cruzi-infected mice are MDSCs. Finally, we found plasma l-arginine depletion in the acute phase of infection that was coincident in time with the appearance of MDSCs, suggesting that in vivo arginase I could be contributing to l-arginine depletion and systemic immunosuppression. Notably, l-arginine supplementation decreased heart tissue parasite load, suggesting that sustained arginase expression through the acute infection is detrimental for the host. This is, to our knowledge, the first time that MDSCs have been found in the heart in the context of myocarditis and also in infection by T. cruzi.

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Role of nitric oxide in resistance and histopathology during experimental infection with Trypanosoma cruzi

Cited by 77 publications

References 28 publications

Infection with different Trypanosoma cruzi populations in rats: myocarditis, cardiac sympathetic denervation, and involvement of digestive organs.

Infection with different Trypanosoma cruzi populations in rats: myocarditis, cardiac sympathetic denervation, and involvement of digestive organs.

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Myeloid-Derived Suppressor Cells Infiltrate the Heart in Acute Trypanosoma cruzi Infection

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