Abstract
•NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91phox −/− or phox KO) were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-γ and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx) at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with •NO in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi.
Highlights
For a long time, reactive oxygen species (ROS) were considered the main anti-microbial radical produced by the immune system, playing a role against bacterial, fungal and protozoa infections
We addressed the role of reactive oxygen species in the resistance to T. cruzi using gene-deficient mice, a species which phagocytes lack the ability to produce
We found that phagocyte-derived reactive oxygen species are not critical to mediate resistance to parasite in the knock-out animals
Summary
Reactive oxygen species (ROS) were considered the main anti-microbial radical produced by the immune system, playing a role against bacterial, fungal and protozoa infections. After the discovery of nitric oxide (NNO), NNO found to play a major role in host defense, especially against protozoan parasites. Since NNO was found to be one of the most important IFN-cinduced anti-parasitic mechanisms, the studies about its role in different diseases was intensified. NNO was found to be crucially important in a variety of infections [10,11], NOS2deficient animals are less susceptible than ifn-c KO to most microorganisms studied [12,13,14,15,16]. The search for other mechanisms of host resistance induced by IFN-c started, and the interest in ROS warmed up again
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