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Activation of the complement cascade by Bordetella pertussis
Michael G Barnes1, Alison A Weiss
1Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, 231 Sabin Way, ML 0524, Cincinnati, OH 45267, USA.
FEMS Microbiology Letters
|April 3, 2003
Summary
Bordetella pertussis evades the human complement system solely through the classical pathway, not alternative or lectin pathways. This resistance is crucial for surviving respiratory tract defenses.
Area of Science:
- Immunology
- Microbiology
- Bacterial Pathogenesis
Background:
- Bordetella pertussis, the causative agent of whooping cough, must evade host immune defenses to establish infection in the respiratory tract.
- The complement system is a critical component of innate immunity that can eliminate bacteria.
- The BrkA protein of B. pertussis is known to confer resistance to complement-mediated killing via the antibody-dependent classical pathway.
Purpose of the Study:
- To investigate the mechanisms by which Bordetella pertussis activates or evades the human complement cascade through antibody-independent pathways.
- To determine if B. pertussis can activate the alternative or lectin pathways of complement.
- To assess the role of lipopolysaccharide (LPS) structure in complement resistance.
Main Methods:
- Bacterial survival assays were performed using human serum depleted of specific complement components (C2, factor B) and antibodies.
- Complement activation pathways were inferred based on bacterial killing efficiency in depleted serum.
- Analysis of complement resistance in B. pertussis mutants lacking the terminal trisaccharide of LPS.
Main Results:
- B. pertussis was resistant to killing in serum lacking C2, indicating the classical pathway was not solely responsible for complement-mediated lysis.
- However, serum depleted of factor B demonstrated efficient killing of B. pertussis, similar to intact serum, strongly suggesting exclusive activation via the classical pathway.
- Absence of bacterial killing in serum depleted of antibodies indicated that B. pertussis does not activate antibody-independent complement pathways, including the mannose-binding lectin pathway.
- Mutants of B. pertussis lacking the terminal trisaccharide of LPS exhibited unchanged resistance to complement, implying this LPS structure is not involved in complement activation.
Conclusions:
- Bordetella pertussis predominantly activates the classical complement pathway in a manner dependent on antibodies.
- The bacteria effectively evade complement-mediated killing through antibody-independent pathways, such as the alternative and mannose-binding lectin pathways.
- The terminal trisaccharide of B. pertussis LPS does not play a significant role in its resistance to complement activation.
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