Pneumolysin (PLY) is a multifunctional pneumococcal virulence factor that appears to augment intrapulmonary growth and dissemination during the early pathogenesis of Streptococcus pneumoniae infection. Through its cytotoxicity to respiratory epithelium and endothelium, PLY disrupts pulmonary tissue barriers that serve as mechanical pulmonary defenses, thus facilitating S. pneumoniae growth and dissemination. Through direct inhibitory effects on immune and inflammatory cells and by activating complement, PLY inhibits bacterial clearance from the pulmonary interstitium and the blood. Because PLY stimulates local and systemic immune responses and enhances the immunogenicity of S. pneumoniae polysaccharide (PS), PLY-PS conjugates may form the basis for vaccines that not only induce protective and durable immune responses to pneumococcal PS but also generate neutralizing anti-PLY antibodies that can protect the respiratory mucosa from toxin-induced injury.
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