C/EBPbeta phosphorylation rescues macrophage dysfunction and apoptosis induced by anthrax lethal toxin

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• Bacillus anthracis lethal toxin (LT) disrupts immune responses.
• LT cleaves MAPK kinases, inhibiting antiapoptotic targets, but these targets remain unidentified.

Purpose of the Study:

• Identify MAPK targets affected by LT.
• Investigate the role of C/EBPbeta in LT-induced macrophage apoptosis and anthrax pathogenesis.

Main Methods:

• Assessed macrophage apoptosis and caspase 8 activation.
• Measured RSK activation and C/EBPbeta phosphorylation.
• Utilized dominant-positive C/EBPbeta transgenic mice for in vivo studies.

Main Results:

• LT induced macrophage apoptosis via enhanced caspase 8 activation and suppressed RSK/C/EBPbeta activation.
• Expression of a phosphorylation mimic C/EBPbeta (C/EBPbeta-E(217)) blocked LT-induced apoptosis.
• LT impaired macrophage phagocytosis and oxidative burst, which was prevented in C/EBPbeta-E(217) transgenic mice.

Conclusions:

• C/EBPbeta is a critical target of LT in macrophages.
• C/EBPbeta plays a significant role in anthrax pathogenesis by regulating macrophage apoptosis and function.