Myeloid-Derived Suppressor Cells Restrain Natural Killer Cell Activity in Acute Coxsackievirus B3-Induced Myocarditis

Area of Science:

• Immunology
• Cardiovascular Research
• Virology

Background:

• Murine models of coxsackievirus B3 (CVB3)-induced myocarditis are crucial for understanding inflammatory heart disease outcomes.
• A.BY/SnJ mice exhibit severe myocarditis with lower natural killer (NK) cell levels compared to C57BL/6 mice.
• Myeloid-derived suppressor cells (MDSC) are implicated in inhibiting NK cells and influencing myocarditis progression.

Purpose of the Study:

• To investigate the interrelationship between MDSC and NK cells in acute CVB3-induced myocarditis.
• To determine the role of MDSC in the pathogenesis of CVB3 myocarditis in A.BY/SnJ mice.

Main Methods:

• Utilized CVB3-infected A.BY/SnJ mice to study MDSC and NK cell interactions.
• Quantified MDSC numbers and S100A8/S100A9 expression in spleen and heart.
• Performed in vitro co-culture experiments to assess MDSC effects on NK cell function.
• Depleted MDSC using an anti-Ly6G antibody and evaluated viral load, cardiac injury, and inflammatory markers.

Main Results:

• Increased MDSC numbers and S100A8/S100A9 expression were observed in the spleen and heart of infected mice.
• In vitro, MDSC disrupted cytotoxic NK cell function.
• MDSC depletion significantly reduced viral load and cardiac injury, with fewer macrophages and T lymphocytes.
• Reduced cardiac expression of S100A8, S100A9, IL-1β, IL-6, and TNF-α was noted in MDSC-depleted mice.

Conclusions:

• Impairment of functional NK cells by MDSC promotes the development of chronic CVB3 myocarditis in A.BY/SnJ mice.
• MDSC play a critical role in CVB3 myocarditis pathogenesis.
• Targeting MDSC may be a potential therapeutic strategy for myocarditis.