Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages.
BACKGROUND:During Trypanosoma cruzi infection, macrophages produce reactive oxygen species (ROS) in a process called respiratory burst. Several works have aimed to elucidate the role of ROS during T. cruzi infection and the results obtained are sometimes contradictory. T. cruzi has a highly efficien...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0004555 https://doaj.org/article/778e1d58502148d49ac1cc9eb1798525 |
id |
ftdoajarticles:oai:doaj.org/article:778e1d58502148d49ac1cc9eb1798525 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:778e1d58502148d49ac1cc9eb1798525 2023-05-15T15:13:17+02:00 Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages. Grazielle R Goes Peter S Rocha Aline R S Diniz Pedro H N Aguiar Carlos R Machado Leda Q Vieira 2016-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004555 https://doaj.org/article/778e1d58502148d49ac1cc9eb1798525 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4818108?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004555 https://doaj.org/article/778e1d58502148d49ac1cc9eb1798525 PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004555 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004555 2022-12-30T22:26:16Z BACKGROUND:During Trypanosoma cruzi infection, macrophages produce reactive oxygen species (ROS) in a process called respiratory burst. Several works have aimed to elucidate the role of ROS during T. cruzi infection and the results obtained are sometimes contradictory. T. cruzi has a highly efficiently regulated antioxidant machinery to deal with the oxidative burst, but the parasite macromolecules, particularly DNA, may still suffer oxidative damage. Guanine (G) is the most vulnerable base and its oxidation results in formation of 8-oxoG, a cellular marker of oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS:In order to investigate the contribution of ROS in T. cruzi survival and infection, we utilized mice deficient in the gp91phox (Phox KO) subunit of NADPH oxidase and parasites that overexpress the enzyme EcMutT (from Escherichia coli) or TcMTH (from T. cruzi), which is responsible for removing 8-oxo-dGTP from the nucleotide pool. The modified parasites presented enhanced replication inside murine inflammatory macrophages from C57BL/6 WT mice when compared with control parasites. Interestingly, when Phox KO macrophages were infected with these parasites, we observed a decreased number of all parasites when compared with macrophages from C57BL/6 WT. Scavengers for ROS also decreased parasite growth in WT macrophages. In addition, treatment of macrophages or parasites with hydrogen peroxide increased parasite replication in Phox KO mice and in vivo. CONCLUSIONS:Our results indicate a paradoxical role for ROS since modified parasites multiply better inside macrophages, but proliferation is significantly reduced when ROS is removed from the host cell. Our findings suggest that ROS can work like a signaling molecule, contributing to T. cruzi growth inside the cells. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 4 e0004555 |
institution |
Open Polar |
collection |
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 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Grazielle R Goes Peter S Rocha Aline R S Diniz Pedro H N Aguiar Carlos R Machado Leda Q Vieira Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:During Trypanosoma cruzi infection, macrophages produce reactive oxygen species (ROS) in a process called respiratory burst. Several works have aimed to elucidate the role of ROS during T. cruzi infection and the results obtained are sometimes contradictory. T. cruzi has a highly efficiently regulated antioxidant machinery to deal with the oxidative burst, but the parasite macromolecules, particularly DNA, may still suffer oxidative damage. Guanine (G) is the most vulnerable base and its oxidation results in formation of 8-oxoG, a cellular marker of oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS:In order to investigate the contribution of ROS in T. cruzi survival and infection, we utilized mice deficient in the gp91phox (Phox KO) subunit of NADPH oxidase and parasites that overexpress the enzyme EcMutT (from Escherichia coli) or TcMTH (from T. cruzi), which is responsible for removing 8-oxo-dGTP from the nucleotide pool. The modified parasites presented enhanced replication inside murine inflammatory macrophages from C57BL/6 WT mice when compared with control parasites. Interestingly, when Phox KO macrophages were infected with these parasites, we observed a decreased number of all parasites when compared with macrophages from C57BL/6 WT. Scavengers for ROS also decreased parasite growth in WT macrophages. In addition, treatment of macrophages or parasites with hydrogen peroxide increased parasite replication in Phox KO mice and in vivo. CONCLUSIONS:Our results indicate a paradoxical role for ROS since modified parasites multiply better inside macrophages, but proliferation is significantly reduced when ROS is removed from the host cell. Our findings suggest that ROS can work like a signaling molecule, contributing to T. cruzi growth inside the cells. |
format |
Article in Journal/Newspaper |
author |
Grazielle R Goes Peter S Rocha Aline R S Diniz Pedro H N Aguiar Carlos R Machado Leda Q Vieira |
author_facet |
Grazielle R Goes Peter S Rocha Aline R S Diniz Pedro H N Aguiar Carlos R Machado Leda Q Vieira |
author_sort |
Grazielle R Goes |
title |
Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages. |
title_short |
Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages. |
title_full |
Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages. |
title_fullStr |
Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages. |
title_full_unstemmed |
Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages. |
title_sort |
trypanosoma cruzi needs a signal provided by reactive oxygen species to infect macrophages. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004555 https://doaj.org/article/778e1d58502148d49ac1cc9eb1798525 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004555 (2016) |
op_relation |
http://europepmc.org/articles/PMC4818108?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004555 https://doaj.org/article/778e1d58502148d49ac1cc9eb1798525 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004555 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
10 |
container_issue |
4 |
container_start_page |
e0004555 |
_version_ |
1766343864090624000 |