NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection.
(•)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...
Published in: | PLoS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:55879e9d239640dcb59d0756a8020d6c 2023-05-15T15:11:24+02:00 NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. Helton C Santiago Claudia Z Gonzalez Lombana Juan P Macedo Lara Utsch Wagner L Tafuri Maria José Campagnole-Santos Rosana O Alves José C F Alves-Filho Alvaro J Romanha Fernando Queiroz Cunha Mauro M Teixeira Rafael Radi Leda Q Vieira 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001492 https://doaj.org/article/55879e9d239640dcb59d0756a8020d6c EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3279332?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001492 https://doaj.org/article/55879e9d239640dcb59d0756a8020d6c PLoS Neglected Tropical Diseases, Vol 6, Iss 2, p e1492 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001492 2022-12-31T12:24:14Z (•)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 (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-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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 2 e1492 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Helton C Santiago Claudia Z Gonzalez Lombana Juan P Macedo Lara Utsch Wagner L Tafuri Maria José Campagnole-Santos Rosana O Alves José C F Alves-Filho Alvaro J Romanha Fernando Queiroz Cunha Mauro M Teixeira Rafael Radi Leda Q Vieira NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
(•)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 (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-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. |
format |
Article in Journal/Newspaper |
author |
Helton C Santiago Claudia Z Gonzalez Lombana Juan P Macedo Lara Utsch Wagner L Tafuri Maria José Campagnole-Santos Rosana O Alves José C F Alves-Filho Alvaro J Romanha Fernando Queiroz Cunha Mauro M Teixeira Rafael Radi Leda Q Vieira |
author_facet |
Helton C Santiago Claudia Z Gonzalez Lombana Juan P Macedo Lara Utsch Wagner L Tafuri Maria José Campagnole-Santos Rosana O Alves José C F Alves-Filho Alvaro J Romanha Fernando Queiroz Cunha Mauro M Teixeira Rafael Radi Leda Q Vieira |
author_sort |
Helton C Santiago |
title |
NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. |
title_short |
NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. |
title_full |
NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. |
title_fullStr |
NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. |
title_full_unstemmed |
NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. |
title_sort |
nadph phagocyte oxidase knockout mice control trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001492 https://doaj.org/article/55879e9d239640dcb59d0756a8020d6c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 2, p e1492 (2012) |
op_relation |
http://europepmc.org/articles/PMC3279332?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001492 https://doaj.org/article/55879e9d239640dcb59d0756a8020d6c |
op_doi |
https://doi.org/10.1371/journal.pntd.0001492 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
6 |
container_issue |
2 |
container_start_page |
e1492 |
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1766342258261491712 |