Distinct roles for nitric oxide in resistant C57BL/6 and susceptible BALB/c mice to control Burkholderia pseudomallei infection

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.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.Nitric oxide (NO) is a free radical molecule that can be expressed by several cell types including fibroblasts, hepatocytes, and phagocytes via nitric oxide synthases. NO exhibits many pleiotropic functions, among these microbicidal activity, and a role in immune regulation are of special interest after infection with parasites, bacteria or viruses. Release of NO can restrict the growth of several pathogens in the host [1-5], but is also known to cause nonspecific damage in host cells that can lead to an exacerbation after infection [2,6]. A rather protective or damaging function for NO was also described to be dependent on the stage of infection or the background mouse strain in several murine infection models [4,6-9].Burkholderia pseudomallei comprises a facultative intracellular gram-negative rod and is the causative agent of melioidosis, an emerging infectious disease of humans an