Artículos de revistas
NADPH Phagocyte Oxidase Knockout Mice Control Trypanosoma cruzi Proliferation, but Develop Circulatory Collapse and Succumb to Infection
Fecha
2012Registro en:
PLOS NEGLECTED TROPICAL DISEASES, SAN FRANCISCO, v. 6, n. 2, pp. 102-110, FEB, 2012
1935-2727
10.1371/journal.pntd.0001492
Autor
Santiago, Helton C.
Lombana, Claudia Z. Gonzalez
Macedo, Juan P.
Utsch, Lara
Tafuri, Wagner L.
Campagnole-Santos, Maria Jose
Alves, Rosana O.
Filho, José Carlos Farias Alves
Romanha, Alvaro J.
Cunha, Fernando Queiroz
Teixeira, Mauro M.
Radi, Rafael
Vieira, Leda Q.
Institución
Resumen
(NO)-N-center dot 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 (gp91(phox-/-) 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-gamma 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)-N-center dot 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.