Cargando…

The Bordetella pertussis adenylate cyclase toxin binds to T cells via LFA-1 and induces its disengagement from the immune synapse

The Bordetella pertussis adenylate cyclase toxin (CyaA) assists infection by potently suppressing the host immune response. Although CyaA effectively targets T lymphocytes, its putative receptor on these cells is unknown. Here, we show that CyaA binds to T cells via the β(2) integrin LFA-1 in its ac...

Descripción completa

Detalles Bibliográficos
Autores principales: Paccani, Silvia Rossi, Finetti, Francesca, Davi, Marilyne, Patrussi, Laura, D'Elios, Mario M., Ladant, Daniel, Baldari, Cosima T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173238/
https://www.ncbi.nlm.nih.gov/pubmed/21576384
http://dx.doi.org/10.1084/jem.20101558
Descripción
Sumario:The Bordetella pertussis adenylate cyclase toxin (CyaA) assists infection by potently suppressing the host immune response. Although CyaA effectively targets T lymphocytes, its putative receptor on these cells is unknown. Here, we show that CyaA binds to T cells via the β(2) integrin LFA-1 in its active conformation. CyaA clusters with LFA-1 at the immune synapse (IS), from which it induces the premature disengagement of LFA-1 concomitant with the dissipation of talin, which tethers the integrin to the underlying actin cytoskeleton. The CyaA-induced redistribution of LFA-1 was cAMP- and protein kinase A (PKA)–dependent. These results not only identify LFA-1 as a CyaA receptor on T cells but unveil a novel mechanism of immunosuppression whereby the toxin parasitizes its interaction with LFA-1 to inhibit signaling at the IS through the local production of cAMP. The data also provide novel insights into the role of cAMP/PKA signaling in controlling the dynamics of the IS.