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Background  Neutrophil extracellular traps (NETs) are a central player in the host response to bacteria: neutrophils release extracellular DNA (nucleosomes) and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs in  Burkholderia pseudomallei  infection (melioidosis), an important cause of Gram-negative sepsis in Southeast Asia.    Methods  In a prospective observational study, circulating nucleosomes and neutrophil elastase were assayed in 44 patients with Gram-negative sepsis caused by  B. pseudomallei  (melioidosis) and 82 controls. Functional assays included human neutrophil stimulation and killing assays and a murine model of  B. pseudomallei  infection in which NET function was compromised using DNase. Specified pathogen-free 8- to 12-week-old C57BL/6 mice were sacrificed post-infection to assess bacterial loads, inflammation, and pathology.    Results  Nucleosome and neutrophil elastase levels were markedly elevated in patients compared to controls. NETs killed  B. pseudomallei  effectively, and neutrophils stimulated with  B. pseudomallei  showed increased elastase and DNA release in a time- and dose-dependent matter. In mice, NET disruption with intravenous DNase administration resulted in decreased nucleosome levels. Although DNase treatment of mice resulted in diminished liver inflammation, no differences were observed in bacterial dissemination or systemic inflammation.    Conclusion   B. pseudomallei  is a potent inducer of NETosis which was reflected by greatly increased levels of NET-related components in melioidosis patients. Although NETs exhibited antibacterial activity against  B. pseudomallei , NET formation did not protect against bacterial dissemination and inflammation during  B. pseudomallei -induced sepsis.    Electronic supplementary material  The online version of this article (doi:10.1186/s40635-014-0021-2) contains supplementary material, which is available to authorized users.

Neutrophil extracellular traps in the host defense against sepsis induced by Burkholderia pseudomallei (melioidosis)