a | Pertussis toxin (PT; Protein Data Bank (PDB) accession 1PRT) is an AB5-type toxin that is composed of one catalytic subunit (the A subunit) and five membrane-binding or transport subunits (the B pentamer)47. PT is assembled in the bacterial periplasm and exported by a type IV secretion system. b | Following binding to a sialoglycoprotein host cell receptor, PT is endocytosed and trafficked through the Golgi apparatus to the endoplasmic reticulum (ER). In the ER, the B pentamer binds to ATP and dissociates from the A subunit. The A subunit is then transported into the cytoplasm and traffics on exosomes to the cytoplasmic membrane, where it ADP-ribosylates the α-subunit of heterotrimeric G proteins. This modification alters the ability of G proteins to regulate multiple enzymes and pathways, including their ability to inhibit cyclic AMP (cAMP) formation. The overall result of these modifications is an initial suppression of inflammatory cytokine production and an inhibition of immune cell recruitment to the site of infection. c | Bordetella adenylate cyclase toxin (ACT) is composed of two primary domains: a calmodulin-responsive adenylate cyclase enzymatic domain and an RTX (repeats in toxin) domain, which are connected by hydrophobic segments. d | The RTX domain of ACT interacts with complement receptor 3 (CR3), which is expressed on host cell membranes from a wide range of cell types. The hydrophobic segments of the linker region form pores in the membrane, enabling the passage of cations and the adenylate cyclase domain is translocated into the cytoplasm. These two activities are mediated by distinct conformations of ACT. Adenylate cyclase activity is stimulated by binding to calmodulin in the host cell, leading to an increase in cAMP production. The combined effects of ACT intoxication and pore formation result in inhibition of complement-dependent phagocytosis, induction of anti-inflammatory cytokines, suppression of pro-inflammatory cytokines and inhibition of immune cell recruitment.