Interleukin-27-dependent transcriptome signatures during neonatal sepsis.

Area of Science:

• Immunology
• Neonatal research
• Infectious disease

Background:

• Human newborns have immature immune systems, increasing infection susceptibility and mortality.
• Interleukin-27 (IL-27), an immune-suppressive cytokine, is elevated in neonatal cells and tissues.
• IL-27 signaling plays a critical role in neonatal immune responses to infection.

Purpose of the Study:

• To investigate the role of IL-27 signaling in neonatal sepsis.
• To explore host response reprogramming in the absence of IL-27 signaling.
• To identify therapeutic strategies for neonatal infections.

Main Methods:

• Utilized a murine model of Escherichia coli-induced neonatal sepsis.
• Compared wild-type (WT) and IL-27 receptor alpha-deficient (IL-27Rα KO) mice.
• Performed transcriptome profiling of neonatal spleens and isolated myeloid populations (macrophages).

Main Results:

• IL-27Rα KO mice exhibited reduced sepsis mortality, improved weight gain, and better bacterial control compared to WT mice.
• Transcriptome analysis revealed differential gene expression, with key inflammatory genes upregulated in WT but not KO neonates.
• Macrophages were identified as a key innate myeloid population contributing to the inflammatory profile in septic WT neonates.

Conclusions:

• Absence of IL-27 signaling improves pathogen clearance with reduced inflammation in neonatal sepsis.
• IL-27 signaling is directly linked to bacterial killing capacity.
• Antagonizing IL-27 presents a promising host-directed therapeutic approach for neonatal infections.