CD155 blockade improves survival in experimental sepsis by reversing dendritic cell dysfunction

Area of Science:

• Immunology
• Infectious Diseases
• Cell Biology

Background:

• Sepsis is characterized by immunosuppression, hindering infection clearance and increasing secondary infection risk.
• Dendritic cells (DCs) and T cells play critical roles in immune regulation during sepsis.

Purpose of the Study:

• To investigate the role of CD155 and TIGIT in sepsis-induced immunosuppression.
• To evaluate the therapeutic potential of targeting CD155 in sepsis models.

Main Methods:

• Analysis of CD155 and TIGIT expression in septic mice.
• Treatment of mouse sepsis models with anti-CD155 antibody.
• Assessment of bacterial burden, cytokine levels (TNF-a, IL-6, IL-10), and DC maturation markers.

Main Results:

• CD155 on DCs and TIGIT on T cells were significantly upregulated in septic mice.
• Anti-CD155 antibody treatment improved survival, reduced bacterial load, and modulated cytokine profiles (increased TNF-a, IL-6; decreased IL-10).
• Overexpression of CD155 on DCs increased IL-10 production and decreased IL-12p40/IL-12p70, indicating an immunosuppressive effect.

Conclusions:

• Increased CD155 expression on DCs contributes to sepsis-induced immunosuppression.
• Targeting CD155 represents a potential therapeutic strategy for improving outcomes in sepsis.