Roles for phagocytic cells and complement in controlling relapsing fever infection

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Relapsing fever spirochetes, like Borrelia hermsii, cause high-level bloodstream infections.
• Mechanisms of B. hermsii survival and immune control in hosts are poorly understood.
• Previous hypotheses suggested complement resistance via factor H binding.

Purpose of the Study:

• To investigate the role of complement and host immune cells in controlling Borrelia hermsii infections.
• To elucidate the mechanisms underlying B. hermsii pathogenesis and host immune response.

Main Methods:

• Utilized complement factor H knockout (Cfh-/-) mice and wild-type mice for infection studies.
• Assessed bacterial levels and factor H adherence in vivo.
• Conducted in vitro complement-mediated inactivation assays.
• Depleted macrophages (mphi) and dendritic cells (DC) in mice to evaluate their role.
• Used muMT mice to investigate antibody-independent immune functions.

Main Results:

• Cfh-/- mice showed infection levels identical to wild-type mice, refuting complement resistance hypothesis.
• Factor H adherence to B. hermsii in wild-type mice was minimal.
• Complement played a role in antibody-mediated inactivation in vitro but was not essential in vivo.
• Depletion of mphi and DC led to uncontrolled infections and mortality.
• muMT studies revealed a significant antibody-independent role for mphi and/or DC.

Conclusions:

• Macrophages and dendritic cells are critical for controlling Borrelia hermsii bloodstream infections.
• These immune cells are essential for producing B. hermsii-specific IgM.
• mphi and/or DC mediate both antibody-dependent and antibody-independent control of spirochetemia.