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

Abstract

Septicemia is the most severe form of melioidosis caused by the Gram-negative bacterium, Burkholderia pseudomallei. Here, we showed 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, monocytes/macrophages and neutrophils were the major source of IL-27 during infection. Addition of exogenous IL-27 in vitro resulted in significantly increased bacterial survival, reduced B. pseudomallei-induced oxidative burst and enhanced IL-1beta and TNF-alpha 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-1beta, but not TNF-alpha production. These results indicate a potential role of IL-27 in suppression of antibacterial defense mechanisms that might contribute to disease severity in sepsis. The targeting of this cytokine may be beneficial in the management of human sepsis.

IL-27 enhances Leishmania amazonensis infection via ds-RNA dependent kinase (PKR) and IL-10 signaling

“…In accordance with the above mentioned dual role of IL-27 in Leishmania infection are our in vivo results, which show augmented parasite loads due to IL-27 treatment, while the lesion sizes were comparable in both groups after the fourth week of infection. Interestingly, a recent report showed that IL-27 enhanced the survival of the Gram-negative bacterium Burkholderia pseudomallei by depressing microbicidal cellular mechanisms (Rinchai et al, 2012). This underlies, together with our findings, the possible significant ability of IL-27 to modulate infections caused by a diversity of different pathogens.…”

IL-27 controls sepsis-induced impairment of lung antibacterial host defence

“…IL-27 has been identified as a vital modulator of immune responses in T cells,12 14 15 and it also regulates biological functions of other immune effector cells, such as macrophages and neurtophils 13 16 17…”

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

“…This observation was supported by our finding in vitro of greater PD-L1 expression on PMNs after coculture with PBMCs than PMNs alone, where IFN-g is produced and secreted by T cells in response to polyclonal activator. We have shown that IL-27 could be produced by PMNs during bacterial infection (35), and IL-27 priming of naive T cells upregulated expression of PD-L1 (36), suggesting that IL-27 from B. pseudomallei-infected PMNs may also contribute to PD-L1 expression on PMNs.…”