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Published on: July 31, 2019
Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice
Carolina Panis1, Vanessa Jacob Victorino1,2, Vera Lúcia Hideko Tatakihara2
1Laboratório de Mediadores Inflamatórios, Universidade Estadual do Oeste do Paraná, Francisco Beltrão, Paraná 85605-010, Brazil.
Abstract:
Infection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO-/-) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of T. cruzi infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO-/- mice during T. cruzi infection. iNOS inhibition generated a remarkable increase in T. cruzi infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN-γ production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward T. cruzi infection.
Insights
Nitric oxide (NO) plays a crucial role in fighting Trypanosoma cruzi infection. Constitutive nitric oxide synthase (cNOS) enhances host resistance and reduces parasite load in the heart during Chagas disease.
Area of Science:
- Immunology
- Parasitology
- Cardiovascular Research
Background:
- Trypanosoma cruzi infection causes Chagas disease, leading to severe heart inflammation.
- Mechanisms driving the inflammatory response in Chagas disease remain unclear.
- Nitric oxide (NO) is vital for parasite clearance, with leukotrienes (LTs) potentially regulating its cardiac activity.
Purpose of the Study:
- To investigate the roles of inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) in heart injury, cytokine profiles, and oxidative stress during early T. cruzi infection.
- To explore the host resistance mechanisms in 5-lipoxygenase-deficient (5-LO-/-) mice infected with T. cruzi.
Main Methods:
- Utilized 5-lipoxygenase-deficient (5-LO-/-) mice infected with Trypanosoma cruzi.
- Administered inhibitors for iNOS and cNOS to assess their impact on infection and host response.
- Analyzed cardiac parasitism, cytokine production (IFN-γ), and lipid peroxidation.
Main Results:
- iNOS inhibition significantly increased T. cruzi infection in blood and heart.
- cNOS inhibition reduced cardiac parasite burden (amastigote nests).
- cNOS inhibition correlated with increased IFN-γ production and decreased lipid peroxidation.
Conclusions:
- Host cNOS contributes to resistance against T. cruzi infection in 5-LO-/- mice.
- Modulating NO pathways, particularly cNOS, may offer therapeutic strategies for Chagas disease.
- Understanding NO's role is key for developing effective treatments for T. cruzi-induced inflammation.
