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.

ROSSI PACCANI, S., Finetti, F., Davi, M., Patrussi, L., Delios, M.m., Ladant, D., et al. (2011). The adenylate cyclase toxin of Bordetella pertussis binds to T cells via the integrin LFA-1 and induces its disengagement from the immune synapse. JOURNAL OF EXPERIMENTAL MEDICINE, 208, 1317-1330.

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

ROSSI PACCANI, SILVIA;FINETTI, FRANCESCA;PATRUSSI, LAURA;DELIOS MM;BALDARI, COSIMA
2011-01-01

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.
ROSSI PACCANI, S., Finetti, F., Davi, M., Patrussi, L., Delios, M.m., Ladant, D., et al. (2011). The adenylate cyclase toxin of Bordetella pertussis binds to T cells via the integrin LFA-1 and induces its disengagement from the immune synapse. JOURNAL OF EXPERIMENTAL MEDICINE, 208, 1317-1330.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/21434
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