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

Hanna K. de Jong*, G. C.K.W. Koh, Ahmed Achouiti, Anne J. van der Meer, Ingrid Bulder, Femke Stephan, J. J.T.H. Roelofs, N. P.J. Day, Sharon J. Peacock, Sacha Zeerleder, W. Joost Wiersinga

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Article number21
Pages (from-to)1-15
Number of pages15
JournalIntensive Care Medicine Experimental
Issue number1
Publication statusPublished - 1 Dec 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014, de Jong et al.; licensee Springer.


  • Burkholderia pseudomallei
  • Diabetes
  • DNase
  • Innate immunity
  • Melioidosis
  • Neutrophil extracellular traps (NETs)
  • Neutrophils
  • Sepsis
  • Survival


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