The adenylate cyclase toxin (CyaA) of Bordetella pertussis is a major virulence factor required for the early phases of lung colonization. It can invade eukaryotic cells where, upon activation by endogenous calmodulin, it catalyzes the formation of unregulated cAMP levels. CyaA intoxication leads to evident toxic effects on macrophages and neutrophils. Here, we demonstrate that CyaA uses the αMβ2 integrin (CD11b/CD18) as a cell receptor. Indeed, the saturable binding of CyaA to the surface of various hematopoietic cell lines correlated with the presence of the αMβ2 integrin on these cells. Moreover, binding of CyaA to various murine cell lines and human neutrophils was specifically blocked by anti-CD11b monoclonal antibodies. The increase of intracellular cAMP level and cell death triggered by CyaA intoxication was also specifically blocked by anti-CD11b monoclonal antibodies. In addition, CyaA bound efficiently and triggered intracellular cAMP increase and cell death in Chinese hamster ovary cells transfected with αMβ2 (CD11b/CD18) but not in cells transfected with the vector alone or with the αXβ2 (CD11c/CD18) integrin. Thus, the cellular distribution of CD11b, mostly on neutrophils, macrophages, and dendritic and natural killer cells, supports a role for CyaA in disrupting the early, innate antibacterial immune response.
Skip Nav Destination
Article navigation
7 May 2001
Article|
April 30 2001
The Adenylate Cyclase Toxin of Bordetella pertussis Binds to Target Cells via the αMβ2 Integrin (Cd11b/Cd18)
Pierre Guermonprez,
Pierre Guermonprez
aUnit of Biology of Immune Regulations, Institut Pasteur,
Search for other works by this author on:
Nadia Khelef,
Nadia Khelef
bUnit of Bordetella, Institut Pasteur,
Search for other works by this author on:
Eric Blouin,
Eric Blouin
dUnit 507, Institut National de la Santé et de la Recherche Medicale (INSERM), Department of Nephrology, Necker Hospital, Paris 75015, France
Search for other works by this author on:
Philippe Rieu,
Philippe Rieu
dUnit 507, Institut National de la Santé et de la Recherche Medicale (INSERM), Department of Nephrology, Necker Hospital, Paris 75015, France
Search for other works by this author on:
Paola Ricciardi-Castagnoli,
Paola Ricciardi-Castagnoli
eDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Milano 20126, Italy
Search for other works by this author on:
Nicole Guiso,
Nicole Guiso
bUnit of Bordetella, Institut Pasteur,
Search for other works by this author on:
Daniel Ladant,
Daniel Ladant
cUnit of Cellular Biochemistry, Institut Pasteur,
Search for other works by this author on:
Claude Leclerc
Claude Leclerc
aUnit of Biology of Immune Regulations, Institut Pasteur,
Search for other works by this author on:
Pierre Guermonprez
aUnit of Biology of Immune Regulations, Institut Pasteur,
Nadia Khelef
bUnit of Bordetella, Institut Pasteur,
Eric Blouin
dUnit 507, Institut National de la Santé et de la Recherche Medicale (INSERM), Department of Nephrology, Necker Hospital, Paris 75015, France
Philippe Rieu
dUnit 507, Institut National de la Santé et de la Recherche Medicale (INSERM), Department of Nephrology, Necker Hospital, Paris 75015, France
Paola Ricciardi-Castagnoli
eDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Milano 20126, Italy
Nicole Guiso
bUnit of Bordetella, Institut Pasteur,
Daniel Ladant
cUnit of Cellular Biochemistry, Institut Pasteur,
Claude Leclerc
aUnit of Biology of Immune Regulations, Institut Pasteur,
Abbreviations used in this paper: CHO; Chinese hamster ovary; FHA, filamentous hemagglutinin; FSDC, fetal mouse skin dendritic cell; LDH, lactate dehydrogenase; MFI, mean fluorescence intensity.
Received:
December 13 2000
Revision Requested:
March 14 2001
Accepted:
March 20 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 193 (9): 1035–1044.
Article history
Received:
December 13 2000
Revision Requested:
March 14 2001
Accepted:
March 20 2001
Citation
Pierre Guermonprez, Nadia Khelef, Eric Blouin, Philippe Rieu, Paola Ricciardi-Castagnoli, Nicole Guiso, Daniel Ladant, Claude Leclerc; The Adenylate Cyclase Toxin of Bordetella pertussis Binds to Target Cells via the αMβ2 Integrin (Cd11b/Cd18). J Exp Med 7 May 2001; 193 (9): 1035–1044. doi: https://doi.org/10.1084/jem.193.9.1035
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement