title: Activation of NADPH oxidase is essential, but not sufficient, in controlling intracellular multiplication of Burkholderia pseudomallei in primary human monocytes.
abstract: Burkholderia pseudomallei is a Gram-negative intracellular bacterium and the causative agent of melioidosis. Innate immune mechanisms against this pathogen, which might contribute to outcomes of melioidosis, are little known. We demonstrated here that B. pseudomallei could activate NADPH oxidase in primary human monocytes as judged by production of reactive oxygen species (ROS) and p40(phox) phosphorylation after infection. However, as similar to other intracellular bacteria, this bacterium was able to resist and multiply inside monocytes despite being able to activate NADPH oxidase. In the presence of NADPH oxidase inhibitor, diphenyleneiodonium or apocynin, intracellular multiplication of B. pseudomallei was significantly increased, suggesting that NADPH oxidase-mediated ROS production is essential in suppressing intracellular multiplication of B. pseudomallei. Additionally, interferon-γ (IFN-γ)-mediated intracellular killing of B. pseudomallei requires NADPH oxidase activity, even though ROS level was not detected at higher levels in IFN-γ-treated infected monocytes. Altogether, these results imply that the activation of NADPH plays an essential role in suppressing intracellular multiplication of B. pseudomallei in human monocytes, although this enzyme is not sufficient to stop intracellular multiplication.
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Chanthiwa
authors.initials: C
authors.lastname: Wikraiphat
authors.forename: Matsayapan
authors.initials: M
authors.lastname: Pudla
authors.forename: Pankaj
authors.initials: P
authors.lastname: Baral
authors.forename: Sangvorn
authors.initials: S
authors.lastname: Kitthawee
authors.forename: Pongsak
authors.initials: P
authors.lastname: Utaisincharoen
mesh_terms: D016957:Burkholderia pseudomallei / Q000254:growth & development* / Q000276:immunology; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D019255:NADPH Oxidases / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D017382:Reactive Oxygen Species; D000072000:NF-KappaB Inhibitor alpha; D019255:NADPH Oxidases
keywords: Burkholderia pseudomallei; NADPH oxidase; monocytes; reactive oxygen species