Production of interleukin-27 by human neutrophils regulates their function during bacterial infection


Rinchai, D; Khaenam, P; Kewcharoenwong, C; Buddhisa, S; Pankla, R; Chaussabel, D; Bancroft, GJ; Lertmemongkolchai, G; (2012) Production of interleukin-27 by human neutrophils regulates their function during bacterial infection. European journal of immunology, 42 (12). pp. 3280-3290. ISSN 0014-2980 DOI: 10.1002/eji.201242526

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Abstract

Septicemia is the most severe form of melioidosis caused by the Gram-negative bacterium, Burkholderia pseudomallei. Here, we show that levels of IL-27p28 transcript and protein were both significantly elevated in patients with sepsis, particularly melioidosis and in patients with unfavorable disease outcome. Moreover, human monocytes/macrophages and neutrophils were the major source of IL-27 during infection. The addition of exogenous IL-27 in vitro resulted in significantly increased bacterial survival, reduced B. pseudomallei-induced oxidative burst, and enhanced IL-1 beta and TNF-a production by purified neutrophils from healthy subjects. Finally, blockade of endogenous IL-27 in neutrophils using soluble IL-27 receptor antagonist prior to infection led to significantly reduced survival of bacteria and decreased IL-1 beta, but not TNF-a production. These results indicate a potential role for IL-27 in the suppression of anti-bacterial defense mechanisms that might contribute to disease severity in sepsis. The targeting of this cytokine may be beneficial in the management of human sepsis.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 22965735
Web of Science ID: 312547800024
URI: http://researchonline.lshtm.ac.uk/id/eprint/612309

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