Acute LPS exposure enhances susceptibility to peripheral prion infection

Area of Science:

• Neuroscience
• Immunology
• Infectious Diseases

Background:

• Prion diseases require initial prion accumulation in secondary lymphoid tissues after peripheral infection for brain transmission.
• Macrophages are thought to sequester or destroy prions, but their role in peripheral prion infection susceptibility is unclear.
• Inflammation can induce a macrophage disappearance reaction in the peritoneal cavity, temporarily sequestering macrophages.

Purpose of the Study:

• To investigate the impact of the lipopolysaccharide (LPS)-induced macrophage disappearance reaction on susceptibility to intraperitoneal prion infection.
• To understand how altered macrophage abundance affects prion propagation and disease transmission.

Main Methods:

• Mice were injected with bacterial lipopolysaccharide (LPS) 24-72 hours before intraperitoneal prion infection.
• Macrophage abundance in the peritoneal cavity was assessed at the time of infection.
• Early prion accumulation in the spleen was quantified to assess prion propagation.

Main Results:

• Intraperitoneal LPS injection increased prion disease susceptibility approximately 100-fold.
• LPS treatment led to reduced macrophage abundance in the peritoneal cavity at the time of prion infection.
• Enhanced early prion accumulation was observed in the spleen following LPS treatment.

Conclusions:

• Reduced peritoneal macrophage abundance after acute LPS treatment enhances prion disease susceptibility.
• This increased susceptibility is likely due to enhanced prion propagation from the peritoneal cavity to the spleen.
• Findings suggest potential for macrophage-targeted therapies to reduce susceptibility to peripherally acquired prion infections.