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

Area of Science:

• Immunology
• Infectious Diseases
• Microbiology

Background:

• Melioidosis, a severe sepsis form caused by Burkholderia pseudomallei, presents significant clinical challenges.
• Understanding host immune responses is crucial for developing effective sepsis therapies.

Purpose of the Study:

• To investigate the role of Interleukin-27 (IL-27) in sepsis, specifically in melioidosis.
• To determine the impact of IL-27 on bacterial survival and host immune cell function during infection.

Main Methods:

• Quantification of IL-27p28 transcript and protein in sepsis patients.
• In vitro studies using human monocytes/macrophages and neutrophils exposed to IL-27.
• Assessment of bacterial survival, oxidative burst, and cytokine production (IL-1β, TNF-α).
• Inhibition of endogenous IL-27 in neutrophils using a soluble IL-27 receptor antagonist.

Main Results:

• Elevated IL-27p28 levels were observed in sepsis patients, correlating with unfavorable outcomes, especially in melioidosis.
• Human monocytes/macrophages and neutrophils are primary sources of IL-27 during infection.
• Exogenous IL-27 increased bacterial survival and IL-1β/TNF-α production while reducing oxidative burst in neutrophils.
• Blocking IL-27 reduced bacterial survival and IL-1β production, but not TNF-α.

Conclusions:

• IL-27 may suppress anti-bacterial defenses, contributing to sepsis severity.
• Targeting IL-27 presents a potential therapeutic strategy for managing sepsis, including melioidosis.