Acanthamoeba interactions with the blood-brain barrier under dynamic fluid flow

Area of Science:

• Neuroscience
• Infectious Diseases
• Microbiology

Background:

• Acanthamoeba granulomatous encephalitis (AGE) is a fatal infection in immunocompromised individuals.
• The mechanism of blood-brain barrier (BBB) invasion by Acanthamoeba castellanii is not fully understood.

Purpose of the Study:

• To investigate the binding dynamics and BBB disruption mechanisms of Acanthamoeba castellanii under physiological flow conditions.
• To elucidate the role of flow rates and host cell interactions in AGE pathogenesis.

Main Methods:

• Utilized a novel in vitro BBB model simulating physiological flow conditions.
• Quantified Acanthamoeba castellanii binding to host cells at varying flow rates.
• Assessed host cell monolayer disruption and identified key factors involved.

Main Results:

• Increased flow rates decreased Acanthamoeba castellanii binding to host cells, contrasting with static conditions.
• Amoeba binding remained dependent on host mannose, irrespective of flow.
• BBB disruption was independent of direct amoeba binding but critically dependent on secreted serine proteases.

Conclusions:

• Blood-brain barrier breach in AGE is primarily mediated by Acanthamoeba castellanii secreted proteases, not direct binding.
• Understanding these dynamics under physiological conditions offers new therapeutic targets for AGE.
• Modulating physiological parameters presents a potential strategy to improve outcomes for Acanthamoeba infections.