Bordetella adenylate cyclase toxin is a unique ligand of the integrin complement receptor 3

  1. Radim Osicka  Is a corresponding author
  2. Adriana Osickova
  3. Shakir Hasan
  4. Ladislav Bumba
  5. Jiri Cerny
  6. Peter Sebo
  1. Institute of Microbiology of the CAS, Czech Republic
  2. Institute of Biotechnology of the CAS, Czech Republic

Abstract

Integrins are heterodimeric cell surface adhesion and signaling receptors that are essential for metazoan existence. Some integrins contain an I-domain that is a major ligand binding site. The ligands preferentially engage the active forms of the integrins and trigger signaling cascades that alter numerous cell functions. Here we found that the adenylate cyclase toxin (CyaA), a key virulence factor of the whooping cough agent Bordetella pertussis, preferentially binds an inactive form of the integrin complement receptor 3 (CR3), using a site outside of its I-domain. CyaA binding did not trigger downstream signaling of CR3 in human monocytes and CyaA-catalyzed elevation of cAMP effectively blocked CR3 signaling initiated by a natural ligand. This unprecedented type of integrin-ligand interaction distinguishes CyaA from all other known ligands of the I-domain-containing integrins and provides a mechanistic insight into the previously observed central role of CyaA in the pathogenesis of B. pertussis.

Article and author information

Author details

  1. Radim Osicka

    Institute of Microbiology of the CAS, Prague, Czech Republic
    For correspondence
    osicka@biomed.cas.cz
    Competing interests
    The authors declare that no competing interests exist.
  2. Adriana Osickova

    Institute of Microbiology of the CAS, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  3. Shakir Hasan

    Institute of Microbiology of the CAS, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  4. Ladislav Bumba

    Institute of Microbiology of the CAS, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  5. Jiri Cerny

    Institute of Biotechnology of the CAS, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter Sebo

    Institute of Microbiology of the CAS, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Johanna Ivaska, University of Turku, Finland

Publication history

  1. Received: August 11, 2015
  2. Accepted: December 9, 2015
  3. Accepted Manuscript published: December 9, 2015 (version 1)
  4. Version of Record published: February 2, 2016 (version 2)

Copyright

© 2015, Osicka et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Radim Osicka
  2. Adriana Osickova
  3. Shakir Hasan
  4. Ladislav Bumba
  5. Jiri Cerny
  6. Peter Sebo
(2015)
Bordetella adenylate cyclase toxin is a unique ligand of the integrin complement receptor 3
eLife 4:e10766.
https://doi.org/10.7554/eLife.10766
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