ISG15 regulates peritoneal macrophages functionality against viral infection

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Type I interferon (IFN) and IFN-stimulated genes (ISGs) establish antiviral states.
• The ubiquitin-like protein ISG15 is an IFN-induced antiviral factor with incompletely understood mechanisms.

Purpose of the Study:

• To investigate the role of ISG15 in regulating macrophage antiviral immune responses.
• To elucidate the molecular mechanisms underlying ISG15's antiviral functions in macrophages.

Main Methods:

• Utilized ISG15 knockout (KO) mice and their macrophages.
• Assessed macrophage activation, phagocytosis, and programmed cell death following vaccinia virus (VACV) infection.
• Performed co-culture experiments with VACV-infected cells.
• Analyzed AKT protein kinase activation.

Main Results:

• ISG15-/- macrophages showed reduced activation, phagocytic capacity, and programmed cell death upon VACV infection.
• ISG15-deficient peritoneal macrophages failed to phagocytose infected cells and block viral spread in co-cultures.
• These defects were independent of cytokine production but correlated with impaired AKT activation in ISG15 KO macrophages.

Conclusions:

• ISG15 is essential for cellular immune antiviral responses, particularly in regulating macrophage functions.
• Impaired AKT activation is linked to the loss of ISG15's antiviral capabilities.
• Understanding ISG15's antiviral pathways may inform therapies against viral pathogens.