title: The Bordetella pertussis adenylate cyclase toxin binds to T cells via LFA-1 and induces its disengagement from the immune synapse.
abstract: 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 β₂ 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.
authors.affiliation: Department of Evolutionary Biology, University of Siena, 53100 Siena, Italy.
authors.forename: Silvia Rossi
authors.initials: SR
authors.lastname: Paccani
authors.forename: Francesca
authors.initials: F
authors.lastname: Finetti
authors.forename: Marilyne
authors.initials: M
authors.lastname: Davi
authors.forename: Laura
authors.initials: L
authors.lastname: Patrussi
authors.forename: Mario M
authors.initials: MM
authors.lastname: D'Elios
authors.forename: Daniel
authors.initials: D
authors.lastname: Ladant
authors.forename: Cosima T
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology; D001886:Bordetella pertussis / Q000378:metabolism*; D040881:CD11a Antigen / Q000096:biosynthesis; D017252:CD3 Complex / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007107:Immune System; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology*
chemical_list: D037361:Adenylate Cyclase Toxin; D040881:CD11a Antigen; D017252:CD3 Complex; D016169:Lymphocyte Function-Associated Antigen-1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases