Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions

Area of Science:

• Immunology
• Complement System Biology

Background:

• The complement system is crucial for innate immunity.
• Factor H (FH) primarily regulates the alternative pathway.
• Emerging evidence highlights non-canonical roles of FH beyond complement modulation.

Purpose of the Study:

• To investigate the effects of FH, FH-like protein 1 (FHL-1), FH-related (FHR) proteins (FHR-1, FHR-5), and mini-FH on monocytes and neutrophils.
• To explore the non-canonical functions of FH family proteins on innate immune cells.

Main Methods:

• Assessing the binding of FH family proteins to monocytes and neutrophils.
• Evaluating the impact of these proteins on neutrophil functions like NET formation, adherence, and IL-8 production.
• Analyzing monocyte adherence and the secretion of inflammatory cytokines (IL-1β, TNFα, IL-10) in response to FH family proteins.

Main Results:

• FH, FHL-1, FHR-1, FHR-5, and mini-FH bind to both monocytes and neutrophils.
• FH and FHR-1 modulated neutrophil functions, including NET formation and IL-8 production.
• FH, mini-FH, and FHL-1 affected monocyte adherence and cytokine secretion, with varying effects observed for FHR-1 and FHR-5.

Conclusions:

• FH family members exhibit heterogeneous effects on monocyte and neutrophil functions.
• These non-canonical functions impact key aspects of pathogen killing.
• FH-based complement inhibitors like mini-FH may possess additional biological activities beyond complement inhibition, relevant for infection protection and vaccine development.