Intracellular C3 regulates the immune response to infection via NF-κB signaling

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Complement factor C3 is a key serum protein in innate immunity.
• Emerging evidence suggests intracellular roles for C3 in cellular processes.
• Previous work demonstrated intracellular C3's role in bacterial opsonization.

Purpose of the Study:

• To investigate the role of intracellular C3 in cellular immune responses.
• To determine how C3 deficiency affects gene expression and signaling pathways.
• To elucidate the impact of cytosolic C3 on immune receptor expression.

Main Methods:

• Analysis of gene expression in C3-deficient cells.
• Assessment of cytokine secretion.
• Investigation of the NF-κB signaling pathway and Toll-like receptor expression.
• Rescue experiments using non-canonical cytosolic C3.

Main Results:

• C3-deficient cells show altered gene expression impacting immune responses.
• Cytokine secretion is reduced in C3-deficient cells, but restored by cytosolic C3.
• C3 deficiency impairs NF-κB signaling due to decreased Toll-like receptor expression.
• Cytosolic C3 expression restores receptor levels and pathway activation.

Conclusions:

• Intracellular C3 plays a critical role in modulating immune responses.
• Cytosolic C3 influences the expression of pathogen recognition receptors.
• C3 deficiency dysregulates immune signaling, a defect reversible by cytosolic C3.