Fig. 12.3.

Functional interactions of M protein. Bacterial surface-bound M protein contributes to (a) GAS aggregation through homotypic interactions, and (b) evasion of phagocytosis through recruitment of fibrinogen or C4BP to the bacterial surface. Bound fibrinogen is also responsible for recruiting plasmin to the GAS surface, which is associated with a transition from localized to invasive infection. (c) M protein released by neutrophil proteases from the bacterial surface interacts with fibrinogen, and M-fibrinogen complexes activate neutrophils via β₂ integrins along with IgGs that bind to M protein and interact with FcγRII. Activated neutrophils release the vasodilator heparin binding protein (HBP). (d) M-fibrinogen complexes also activate platelets. This occurs through interaction of these complexes with the integrin GPIIb/IIIa along with IgGs that bind to M protein and interact with FcγRII. Activated platelets in turn lead to further activation of neutrophils and monocytes. (e) M protein synergizes in a TLR2-dependent manner with HBP to activate monocytes, which then secrete proinflammatory cytokines and upregulate the procoagulatory protein tissue factor. (f) M protein is also responsible for neutralizing the antimicrobial effects of cathelicidins in neutrophil extracellular traps (NET)