Very late antigen-5 and complement receptor type 3 cooperatively mediate the interaction between Bordetella pertussis and human monocytes.
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.
Hazenbos
W L
WL
Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
van den Berg
B M
BM
van Furth
R
R
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001422:Bacterial Adhesion; D001886:Bordetella pertussis / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D006388:Hemagglutinins / Q000502:physiology; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000382:microbiology*; D017469:Receptors, Fibronectin / Q000502:physiology*; D010566:Virulence Factors, Bordetella
D018829:Adhesins, Bacterial; D000911:Antibodies, Monoclonal; D005353:Fibronectins; D006388:Hemagglutinins; D016177:Macrophage-1 Antigen; D017469:Receptors, Fibronectin; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis