Figure 2.

Roles of pneumococcal proteases at the host cellular level. (a) At least 5 proteases are involved in attachment to nasopharyngeal or lung epithelial cells. (b) Pneumococcal proteases can inhibit complement deposition, as depicted by the abridged classical complement pathway. CppA and histidine triad proteins degrade complement component C3, which is important for pathogen recognition by phagocytes. PepO can bind to C1q, but can also act as a complement activator and promote premature consumption by inhibiting the regulatory inhibitor C4BP. In the presence of uPA, PepO cleaves plasminogen to the proteolytically active plasmin, and plasmin prematurely degrades C3b and inhibits its deposition on S. pneumoniae. Since C3b is necessary for binding to complement receptor on phagocytes such as neutrophils (opsonization), inhibition of C3b deposition contributes to immune evasion