Confounding roles for type I interferons during bacterial and viral pathogenesis

Area of Science:

• Immunology
• Virology
• Microbiology

Background:

• Type I interferons (IFN-I) are primarily known for their potent antiviral functions, including direct viral replication suppression and immune response activation.
• IFN-I also contribute to host defense against extracellular bacteria by promoting TNF-α and nitric oxide induction.
• However, IFN-I can negatively impact host resistance during specific chronic viral and acute intracellular bacterial infections.

Purpose of the Study:

• To review the complex and often contradictory roles of Type I interferons (IFN-I) in host defense against various pathogens.
• To emphasize the need for mechanistic evaluation of IFN-I's role in pathogenesis, particularly during chronic infections.
• To highlight findings from studies using IFN-I-receptor-deficient mice.

Main Methods:

• Review of existing literature on Type I interferons (IFN-I) and their effects on host resistance during different types of infections.
• Analysis of studies investigating IFN-I signaling pathways and their impact on innate and adaptive immunity.
• Emphasis on data from IFN-I-receptor-deficient mouse models to elucidate IFN-I-specific effects.

Main Results:

• Chronic IFN-I signaling suppresses adaptive immunity during lymphocytic choriomeningitis virus (LCMV) infection, with blockade restoring T-cell responses.
• During acute intracellular bacterial infections (e.g., Francisella, Listeria), IFN-I suppress innate immunity.
• IFN-I inhibit IL-17 upregulation and neutrophil recruitment in Francisella infections and promote immune cell death in Listeria infections.

Conclusions:

• Type I interferons (IFN-I) display context-dependent effects on host defense, acting as both protective and detrimental factors.
• The dual role of IFN-I underscores the complexity of the interferon system in host-pathogen interactions.
• Further mechanistic studies are essential to fully understand the impact of IFN-I on pathogenesis and to develop targeted therapeutic strategies.