title: Impact of reactive oxygen species (ROS) on the control of parasite loads and inflammation in Leishmania amazonensis infection.
abstract: BACKGROUND
  Reactive oxygen species (ROS) protect the host against a large number of pathogenic microorganisms. ROS have different effects on parasites of the genus Leishmania: some parasites are susceptible to their action, while others seem to be resistant. The role of ROS in L. amazonensis infection in vivo has not been addressed to date.
  
  
  METHODS
  In this study, C57BL/6 wild-type mice (WT) and mice genetically deficient in ROS production by phagocytes (gp91(phox-/-)) were infected with metacyclic promastigotes of L. amazonensis to address the effect of ROS in parasite control. Inflammatory cytokines, parasite loads and myeloperoxidase (MPO) activity were evaluated. In parallel, in vitro infection of peritoneal macrophages was assessed to determine parasite killing, cytokine, NO and ROS production.
  
  
  RESULTS
  In vitro results show induction of ROS production by infected peritoneal macrophages, but no effect in parasite killing. Also, ROS do not seem to be important to parasite killing in vivo, but they control lesion sizes at early stages of infection. IFN-γ, TNF-α and IL-10 production did not differ among mouse strains. Myeloperoxidase assay showed augmented neutrophils influx 6 h and 72 h post - infection in gp91(phox-/-) mice, indicating a larger inflammatory response in gp91(phox-/-) even at early time points. At later time points, neutrophil numbers in lesions correlated with lesion size: larger lesions in gp91(phox-/-) at earlier times of infection corresponded to larger neutrophil infiltrates, while larger lesions in WT mice at the later points of infection also displayed larger numbers of neutrophils.
  
  
  CONCLUSIONS
  ROS do not seem to be important in L. amazonensis killing, but they regulate the inflammatory response probably by controlling neutrophils numbers in lesions.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.|Current address: Instituto Nacional de Infectologia, Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Eric Henrique
authors.initials: EH
authors.lastname: Roma
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Juan Pereira
authors.initials: JP
authors.lastname: Macedo
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Grazielle Ribeiro
authors.initials: GR
authors.lastname: Goes
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.|Current address: Instituto Nacional de Infectologia, Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Juliana Lauar
authors.initials: JL
authors.lastname: Gonçalves
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.|Current address: Laboratory of Malaria and Vector Research, Vector Molecular Biology Section, National Institutes of Health, NIAID, Rockville, MD, USA.
authors.forename: Waldionê de
authors.initials: Wd
authors.lastname: Castro
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cisalpino
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. lqvieira@icb.ufmg.br.
authors.forename: Leda Quercia
authors.initials: LQ
authors.lastname: Vieira
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology*; D007894:Leishmania mexicana / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D009195:Peroxidase / Q000032:analysis; D017382:Reactive Oxygen Species / Q000633:toxicity*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D009195:Peroxidase
keywords: Inflammation; Leishmania amazonensis; NOX2; Neutrophils; ROS