Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Relapsing fever is a severe septic illness caused by Borrelia spirochetes, with epidemic and endemic forms.
• Borrelia species exhibit immune evasion strategies, persisting in the bloodstream despite antibody development, leading to relapses and high mortality.
• Understanding these immune evasion mechanisms is crucial for developing effective treatments against relapsing fever.

Purpose of the Study:

• To investigate the serum resistance of Borrelia recurrentis (epidemic) and Borrelia duttonii (endemic) relapsing fever pathogens.
• To determine if these spirochetes utilize immune evasion strategies involving complement regulators.
• To identify the specific complement regulators bound by relapsing fever Borrelia species.

Main Methods:

• In vitro assessment of serum resistance (complement resistance) for Borrelia recurrentis and Borrelia duttonii.
• Analysis of the binding of host complement regulators, specifically Factor H and C4b-binding protein, to the surface of these spirochetes.
• Functional assessment of bound complement regulators to confirm their activity.

Main Results:

• Borrelia recurrentis and Borrelia duttonii demonstrated resistance to complement-mediated lysis in vitro.
• Both pathogens were found to acquire the alternative complement pathway regulator, Factor H, onto their surfaces.
• Relapsing fever spirochetes specifically bound the classical complement pathway regulator, C4b-binding protein, which retained its function when bound.

Conclusions:

• This study provides the first evidence of complement evasion mechanisms in Borrelia recurrentis and Borrelia duttonii.
• The capture of host Factor H and C4b-binding protein represents a novel immune evasion strategy employed by these relapsing fever pathogens.
• These findings highlight the sophisticated ways Borrelia spirochetes evade host immune responses, contributing to disease persistence and severity.