Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology

Area of Science:

• Immunology
• Virology
• Dermatology

Background:

• Type III interferons (IFN-λ) are crucial for antiviral immunity, primarily studied in respiratory and gastrointestinal contexts.
• The role of IFN-λ in skin infections, particularly against herpes simplex virus (HSV), remains underexplored.

Approach:

• Investigated the role of IFN-λ in HSV skin infections using knockout mouse models lacking IFN-λ receptors or cytokines.
• Utilized conditional knockout mice to pinpoint the cell-specific roles of IFN-λ signaling in keratinocytes and neutrophils.
• Assessed the impact of IFN-λ on viral load, lesion severity, and immune cell infiltration, specifically neutrophils and CXCL9 chemokine.

Key Points:

• IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions independently of direct viral load reduction.
• IFN-λ signaling in keratinocytes is essential for controlling HSV-1 skin lesion severity by suppressing CXCL9-mediated neutrophil recruitment.
• Neutrophil depletion or CXCL9 blockade ameliorated skin lesions in mice lacking IFN-λ receptors, highlighting a protective immunomodulatory role.

Conclusions:

• IFN-λ exerts an immunomodulatory function in the skin, mitigating pathology during HSV infection by controlling neutrophil responses.
• Findings suggest therapeutic potential for IFN-λ in managing viral skin infections like HSV.