title: Distinct roles for nitric oxide in resistant C57BL/6 and susceptible BALB/c mice to control Burkholderia pseudomallei infection.
abstract: BACKGROUND
  Burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. We recently showed that NADPH oxidase but not nitric oxide (NO) contributes to resistance in innately resistant C57BL/6 mice in a B. pseudomallei respiratory infection model. However, the function of NO for resistance was shown to differ among distinct strains of mice and proved also to be stage dependent in various infection models. The present study therefore aimed to examine the role of NO in a systemic infection model of melioidosis and to test whether the function of NO differs among innately resistant C57BL/6 and susceptible BALB/c mice after B. pseudomallei infection.
  
  
  RESULTS
  C57BL/6 iNOS-/- mice that were intravenously infected with B. pseudomallei survived several weeks, whereas most of the wild type animals succumbed during this period. The bacterial burden in liver and spleen was significantly higher in wild type animals compared to iNOS-/- mice 13 days after challenge. In contrast, BALB/c mice that were treated with amminoguanidine to inhibit NO expression in vivo showed significantly enhanced mortality rates and higher bacterial loads in liver and spleen compared to control animals. The bactericidal function of IFN-γ stimulated C57BL/6 iNOS-/- macrophages were not altered after B. pseudomallei infection, but BALB/c macrophages exhibited reduced killing activity against the pathogen when NO was inhibited.
  
  
  CONCLUSIONS
  Our present data indicate a dual role of NO among resistant and susceptible mouse strains after B. pseudomallei infection. NO mediated mechanisms are an essential component to control the infection in susceptible BALB/c mice. In contrast, NO production in B. pseudomallei infected C57BL/6 mice rather harmed the host likely due to its detrimental effects.
authors.affiliation: Friedrich Loeffler Institute of Medical Microbiology, Ernst Moritz Arndt University Greifswald, Martin-Luther-Strasse 6, 17489 Greifswald, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Breitbach
authors.forename: Patimaporn
authors.initials: P
authors.lastname: Wongprompitak
authors.forename: Ivo
authors.initials: I
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D016957:Burkholderia pseudomallei / Q000276:immunology* / Q000472:pathogenicity; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D019791:Guanidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007110:Immunity, Active; D008262:Macrophage Activation / Q000187:drug effects; D008554:Melioidosis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D013045:Species Specificity
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019791:Guanidine