title: UCP2 deficiency helps to restrict the pathogenesis of experimental cutaneous and visceral leishmaniosis in mice.
abstract: BACKGROUND
  Uncoupling protein 2 (UCP2) is a mitochondrial transporter that has been shown to lower the production of reactive oxygen species (ROS). Intracellular pathogens such as Leishmania upregulate UCP2 and thereby suppress ROS production in infected host tissues, allowing the multiplication of parasites within murine phagocytes. This makes host UCP2 and ROS production potential targets in the development of antileishmanial therapies. Here we explore how UCP2 affects the outcome of cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL) in wild-type (WT) C57BL/6 mice and in C57BL/6 mice lacking the UCP2 gene (UCP2KO).
  
  
  RESULTS
  To investigate the effects of host UCP2 deficiency on Leishmania infection, we evaluated parasite loads and cytokine production in target organs. Parasite loads were significantly lower in infected UCP2KO mice than in infected WT mice. We also found that UCP2KO mice produced significantly more interferon-γ (IFN-γ), IL-17 and IL-13 than WT mice (P<0.05), suggesting that UCP2KO mice are resistant to Leishmania infection.
  
  
  CONCLUSIONS
  In this way, UCP2KO mice were better able than their WT counterparts to overcome L. major and L. infantum infections. These findings suggest that upregulating host ROS levels, perhaps by inhibiting UPC2, may be an effective approach to preventing leishmaniosis.
authors: Department of Animal Health, Veterinary Faculty, Complutense University of Madrid, Madrid, Spain. fjcarrion@vet.ucm.es
authors: Javier
authors: J
authors: Carrión
authors: M Angeles
authors: MA
authors: Abengozar
authors: María
authors: M
authors: Fernández-Reyes
authors: Carlos
authors: C
authors: Sánchez-Martín
authors: Eduardo
authors: E
authors: Rial
authors: Gustavo
authors: G
authors: Domínguez-Bernal
authors: M Mar
authors: MM
authors: González-Barroso
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007473:Ion Channels / Q000172:deficiency*; D018314:Leishmania infantum / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D018320:Leishmania major / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000172:deficiency*; D059208:Parasite Load; D000071246:Uncoupling Protein 2
chemical_list: D016207:Cytokines; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2