Table 2.

Causes of overexuberant inflammatory responses during pneumococcal CAP.

Cause	Consequence
Excessive release of pneumolysin	Uncontrolled complement activation; hyperactivation of phagocytes and epithelial cells due to the noncytolytic, pore-forming actions of the toxin
Excessive release of bacterial cell-wall products (e.g., lipoteichoic acids and DNA), especially during chemotherapy with bactericidal agents	Sustained activation of various types of pathogen recognition receptors on/in cells of the innate immune system and epithelial cells, resulting in poorly regulated production of neutrophil-mobilising chemokines/cytokines
Poorly controlled formation of NETs with limited protective activity	Histone-mediated epithelial and endothelial toxicity, favouring extrapulmonary spread of the pneumococcus
Excessive release of cell-permeable, proinflammatory H2O2 by the pneumococcus	Uncontrolled activation of redox intracellular signalling mechanisms in cells of the innate and adaptive immune systems, as well as other cell types. The existence of this mechanism remains to be established