Role of pneumococcal pneumolysin in the induction of an inflammatory response in human epithelial cells.

Epithelial cells act as the first line of host defense against microorganisms by producing a range of molecules for clearance. Proinflammatory cytokines facilitate the clearance of invaders by the recruitment and activation of leukocytes. Upregulation of cytokine expression thus represents an important host innate defense response against invading microorganisms such as Streptococcus pneumoniae. Histological analysis of the airway revealed less leukocyte infiltration during the early stage of pneumococcal infection, when compared with nontypable Haemophilus influenzae (NTHi) infection. Here, we report that S. pneumoniae is less potent in inducing proinflammatory cytokine expression compared with NTHi. Among numerous virulence factors, pneumococcal pneumolysin was found to be the major factor responsible for the induction of inflammation. Interestingly, pneumolysin induces cytokine expression to a lesser extent at the early stage of infection, but becomes more potent in inducing inflammation at the late stage. Thus, this study reveals that pneumolysin induces the proinflammatory cytokine expression in a time-dependent manner.