An intact complement system dampens cornea inflammation during acute primary HSV-1 infection

Area of Science:

• Ophthalmology
• Immunology
• Virology

Background:

• Corneal transparency is vital for vision.
• Microbial infections like HSV-1 can compromise corneal integrity through inflammation, neovascularization (NV), and tissue damage.
• Previous research linked complement activation to HSV-1-induced corneal denervation.

Purpose of the Study:

• To investigate the role of the complement system, particularly complement component 3 (C3), in HSV-1-mediated corneal neovascularization.
• To determine if C3 deficiency impacts inflammatory cell infiltration and pro-angiogenic factor expression during HSV-1 keratitis.

Main Methods:

• Utilized wild-type (WT) and C3-deficient (C3 KO) mice infected with HSV-1.
• Analyzed corneal neovascularization, inflammatory cell populations (monocytes, macrophages, granulocytes/neutrophils), and expression of inflammatory/angiogenic factors (IL-1α, MMPs, CXCL1, CCL2, VEGF-A).
• Assessed viral titers and viral antigen clearance in corneas.

Main Results:

• Corneal NV was accelerated in C3 KO mice compared to WT mice.
• C3 KO mice exhibited increased infiltration of inflammatory monocytes, macrophages, and neutrophils.
• Elevated levels of pro-inflammatory and pro-angiogenic factors were observed in C3 KO corneas, correlating with increased inflammation, NV, and opacity.
• Viral antigen clearance was impaired in C3 KO mouse corneas, despite similar viral titers between groups.

Conclusions:

• The complement system, via C3, plays a critical regulatory role in controlling HSV-1-induced corneal neovascularization and inflammation.
• C3 deficiency exacerbates corneal pathology by promoting inflammation and angiogenesis and hindering viral clearance.
• Complement activation is essential for effective resolution of HSV-1 keratitis.