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Very late antigen-5 and complement receptor type 3 cooperatively mediate the interaction between Bordetella pertussis
W L Hazenbos1, B M van den Berg, R van Furth
1Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
Abstract:
Nonopsonized Bordetella pertussis, the causative agent of whooping cough, can attach to and become ingested by human monocytes. It has been reported that complement receptor type 3 (CR3) on human monocyte-derived macrophages binds filamentous hemagglutinin expressed on B. pertussis. In the present study, the role of very late antigen-5 (VLA-5) in the attachment of B. pertussis to adherent human monocytes was investigated. It was found that soluble fibronectin and soluble mAb against VLA-5 markedly inhibited the attachment of B. pertussis to monocytes. When VLA-5 on monocytes was cross-linked by plating these cells onto surfaces precoated with fibronectin or mAb against VLA-5, the binding of both B. pertussis and C3bi-coated sheep erythrocytes to these cells was significantly enhanced, whereas the binding of a B. pertussis mutant strain deficient in filamentous hemagglutinin was not affected. The enhanced attachment of B. pertussis to monocytes plated onto fibronectin-coated surfaces was markedly inhibited by soluble mAb against CR3. Neutrophils, which express similar levels of CR3 and about 10-fold lower levels of VLA-5 as compared with monocytes, did not bind B. pertussis. Together, these results indicate that VLA-5 is involved in the attachment of B. pertussis to monocytes and that cross-linking of VLA-5 enhances the attachment of B. pertussis to monocytes by augmenting the binding activity of CR3. We propose that the attachment of B. pertussis to monocytes occurs in two steps: binding and cross-linking of VLA-5 by B. pertussis enhances the binding activity of CR3, which in turn facilitates the subsequent binding of these bacteria to the latter receptor.
Insights
Very late antigen-5 (VLA-5) on monocytes mediates Bordetella pertussis attachment. Cross-linking VLA-5 enhances complement receptor type 3 (CR3) binding, facilitating bacterial adhesion to monocytes during whooping cough infection.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Bordetella pertussis, the whooping cough pathogen, adheres to and is ingested by human monocytes.
- Complement receptor type 3 (CR3) on macrophages binds Bordetella pertussis filamentous hemagglutinin.
Purpose of the Study:
- To investigate the role of very late antigen-5 (VLA-5) in Bordetella pertussis attachment to human monocytes.
- To elucidate the mechanism by which VLA-5 influences bacterial adhesion.
Main Methods:
- Monocyte attachment assays using soluble fibronectin and monoclonal antibodies (mAbs) against VLA-5.
- Cross-linking VLA-5 on monocytes using fibronectin or anti-VLA-5 mAb-coated surfaces.
- Assessing binding of Bordetella pertussis and C3bi-coated sheep erythrocytes.
- Investigating the role of CR3 using anti-CR3 mAb and a Bordetella pertussis mutant strain.
Main Results:
- Soluble fibronectin and anti-VLA-5 mAb inhibited Bordetella pertussis attachment to monocytes.
- Cross-linking VLA-5 enhanced binding of Bordetella pertussis and C3bi-coated erythrocytes, an effect dependent on filamentous hemagglutinin.
- Enhanced attachment was inhibited by anti-CR3 mAb, and neutrophils showed reduced binding compared to monocytes.
Conclusions:
- VLA-5 is crucial for Bordetella pertussis attachment to monocytes.
- VLA-5 cross-linking augments CR3-mediated binding, facilitating bacterial adhesion.
- A two-step model is proposed: VLA-5 binding/cross-linking enhances CR3 activity for subsequent bacterial adherence.