title: Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Grazielle R
authors.initials: GR
authors.lastname: Goes
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Rocha
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Aline R S
authors.initials: AR
authors.lastname: Diniz
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Pedro H N
authors.initials: PH
authors.lastname: Aguiar
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Machado
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Leda Q
authors.initials: LQ
authors.lastname: Vieira
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000469:parasitology; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D004195:Disease Models, Animal; D006790:Host-Parasite Interactions; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012235:Rhodamines / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*
chemical_list: D003848:Deoxyguanine Nucleotides; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D012235:Rhodamines; C058319:dihydrorhodamine 123; C078206:8-oxodeoxyguanosine triphosphate; D006861:Hydrogen Peroxide; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases