Figure 8. CyaA acts as a unique ligand of the I-domain-containing integrin CR3.
CyaA secreted by B. pertussis binds CR3 outside of its I-domain, using a unique site that encompasses the C-terminal end of the last repeat of the β-propeller domain and the N-terminal portion of the thigh domain of CD11b. CyaA preferentially binds the integrin in a non-activated (bent, low-affinity) conformation and engagement of CR3 by CyaA does not trigger Syk activation in monocytes. Moreover, CyaA-catalyzed elevation of cAMP effectively blocks the iC3b opsonin-elicited activation of CR3-Syk signaling in monocytes. It remains to be elucidated how CyaA-produced cAMP signaling suppresses Syk activity. Binding outside of the I-domain in an activation-independent mode thus enables the toxin to hijack CR3 and block its signaling, thereby enabling B. pertussis to evade CR3-mediated phagocytosis.