A genetically encoded reporter reveals interferon responses in multiple cell lineages

Area of Science:

• Immunology
• Neuroscience
• Molecular Biology

Background:

• Interferons (IFNs) are crucial antiviral cytokines with important homeostatic roles in various tissues, including the brain.
• Understanding the full scope of IFN signaling is hindered by a lack of tools to visualize IFN-responsive cells.

Purpose of the Study:

• To develop a novel reporter system for visualizing interferon responses in living cells.
• To characterize the sensitivity and utility of the new reporter system in different biological contexts.

Main Methods:

• Development of the IFN-brite reporter mouse model, utilizing the bright mGreenLantern fluorophore under the control of the interferon-stimulated gene 15 (Isg15) promoter.
• In vivo and in vitro experiments involving cytokine delivery and influenza A infection to assess reporter activity.
• Analysis of IFN-brite signal distribution across various cell types in the brain and lung.

Main Results:

• The IFN-brite reporter is highly sensitive to Interferon-beta (IFN-β) and shows detectable responses to Interferon-gamma (IFN-γ).
• IFN-brite signals were observed in multiple brain cell types, as well as in lung stromal and hematopoietic cells following influenza A infection.
• The reporter system successfully visualized IFN responses in diverse cell types, including immune, stromal, and neuronal cells.

Conclusions:

• IFN-brite is a valuable new tool for studying interferon responses in real-time across various tissues and cell types.
• The findings suggest that a wide range of cell types, including neurons, actively participate in interferon signaling pathways.
• This tool facilitates deeper investigation into the complex roles of interferons in both immunity and tissue homeostasis.