Complement-mediated killing of the Lyme disease spirochete Borrelia burgdorferi. Role of antibody in formation of an effective membrane attack complex
Abstract
Abstract Lyme disease is a multisystemic illness caused by the spirochete Borrelia burgdorferi. In the absence of specific antibody, the spirochete is resistant to the bactericidal activity of C, despite the capacity of B. burgdorferi to activate both C pathways. We examined the mechanism of serum resistance by measuring the deposition of C3 and terminal C components on B. burgdorferi in the presence and absence of immune IgG. In normal human serum antibody-sensitized borreliae bound similar amounts of C3, and similar or increased amounts of C8 and C9, in comparison to unsensitized bacteria. However, at comparable levels of C3, C8, or C9 uptake, only sensitized bacteria were killed. The requirement of antibody for killing could not be explained by differences in the rate of C deposition or by differences in the C9 to C8 ratio in the membrane attack complex (MAC). We found that bacteria incubated in C5-depleted human serum, but not in C6-depleted serum, were killed when this treatment was followed by antibody and the missing C components. Bacteria were also killed by reactive lysis (C5b-9) provided that antibody was present. Therefore, the effect of bactericidal IgG occurred at the stage of C5b binding to the bacterial surface. Elution studies of bound C9 indicated that the MAC was stably bound to the outer membrane of B. burgdorferi, whether or not the bacteria were treated with antibody. However, treatment with 0.1% trypsin released 48% of 125I-C9 from the surface of unsensitized borreliae and 24% from IgG-sensitized cells, demonstrating that the presence of the antibody changed the accessibility to trypsin of C9 in the MAC. These results indicate that the effect of antibody in the killing process is not to enhance the rate or extent of initial or terminal component binding, but rather to alter the bacterial outer membrane to allow effective MAC formation.
Key Biomarkers
Cited By (5)
- LYME DISEASE:A Review of Aspects of Its Immunology and ImmunopathogenesisAnnual Review of Immunology · 1997
- Complement split products C3a and C4a are early markers of acute lyme disease in tick bite patients in the United StatesInternational Archives of Allergy and Immunology · 2008
- Complement evasion by Borrelia burgdorferi: it takes three to tangoTrends in Parasitology · 2004
- Mechanism of complement resistance of pathogenic Borrelia burgdorferi isolatesInternational Immunopharmacology · 2001
- The important and diverse roles of antibodies in the host response to Borrelia infectionsCurrent topics in microbiology and immunology · 2008
Related Papers
- Herbal Therapeutics for CIRS Biomarkers in Autism Spectrum Disorders: A Mechanistic and Molecular Approach for Neuroimmune Pathology in PediatricsMedical Research Archives · 2025 · 2 shared tags
- Exploring Structured Camel Milk Therapy Alongside an Individualised Botanical Support Protocol to Facilitate Immune Modulation in a Child Diagnosed with PANS/PANDAS Co-Morbid with Lyme Disease and AutismJournal of Camel Practice and Research · 2025 · 2 shared tags
- Neuroplasticity Intervention, Amygdala and Insula Retraining (AIR), Significantly Improves Overall Health and Functioning Across Various Chronic Conditions.PubMed · 2023 · 2 shared tags
- Introduction to Chronic Inflammatory Response Syndrome (CIRS)2023 · 2 shared tags
- TUBB1, TUBA4A and MAPK as Indicators of Die-Back Degenerative Central Nervous System Disease in Patients Sickened by Specific Exposure to the Interior Environment of Water- Damaged BuildingsMedical Research Archives · 2023 · 2 shared tags
- Autism Spectrum Disorders and Lyme Disease: Exploring Shared Neuro-Inflammatory and Immune Pathways