IL-1α Modulates IFN-γ-Induced Production of CXCL9/MIG during Herpes Simplex Virus Type-1 Corneal Infection

Area of Science:

• Immunology
• Ophthalmology
• Virology

Background:

• Herpes simplex virus type 1 (HSV-1) causes corneal infections, triggering inflammatory responses.
• Neutrophils play a role in inflammation, producing various pro-inflammatory mediators.
• Chemokines like MIG and IP-10 are crucial for recruiting immune cells to infection sites.

Purpose of the Study:

• To investigate the modulation of neutrophil-derived chemokines MIG and IP-10 during HSV-1 corneal infection.
• To explore the role of interleukin-1 alpha (IL-1α) in regulating these chemokine productions.

Main Methods:

• Utilized an ex vivo human corneal infection model with HSV-1.
• Incorporated human neutrophils to study cytokine production.
• Measured pro-inflammatory mediators using multi-analyte ELISA and quantitative ELISA.
• Employed antibody neutralization of IL-1α to assess its effect on MIG and IP-10.

Main Results:

• HSV-1 infection elevated specific pro-inflammatory mediators (IL-8, IL-6, IL-1α, IL-1β) in corneal cells.
• Neutrophils produced significant MIG and IP-10 upon interferon-gamma (IFN-γ) stimulation.
• MIG production by neutrophils was further upregulated by co-stimulation with IFN-γ and HSV-1.
• Neutralizing IL-1α increased MIG production but did not affect IP-10 production.

Conclusions:

• IL-1α influences the expression patterns of MIG and IP-10 during HSV-1 corneal infection.
• Both corneal cells and neutrophils contribute to T cell-recruiting chemokine production.
• IL-1α differentially regulates MIG production: upregulating it in corneal cells and downregulating it in neutrophils.