Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection

Proceedings of the National Academy of Sciences of the United States of America
Richard MalleyDouglas T Golenbock

Abstract

Streptococcus pneumoniae is one of the leading causes of invasive bacterial disease worldwide. Fragments of the cell wall and the cytolytic toxin pneumolysin have been shown to contribute substantially to inflammatory damage, although the interactions between pneumococcal components and host-cell structures have not been elucidated completely. Results of a previous study indicated that cell-wall components of pneumococci are recognized by Toll-like receptor (TLR)2 but suggested that pneumolysin induces inflammatory events independently of this receptor. In this study we tested the hypothesis that pneumolysin interacts with surface proteins of the TLR family other than TLR2. We found that pneumolysin stimulates tumor necrosis factor-alpha and IL-6 release in wild-type macrophages but not in macrophages from mice with a targeted deletion of the cytoplasmic TLR-adapter molecule myeloid differentiation factor 88, suggesting the involvement of the TLRs in pneumolysin recognition. Purified pneumolysin synergistically activated macrophage responses together with preparations of pneumococcal cell walls or staphylococcal peptidoglycan, which are known to activate TLR2. Furthermore, when compared with wild-type macrophages, macrophages f...Continue Reading

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Related Concepts

PlY protein, Streptococcus pneumoniae
Bacterial Proteins
Flow Cytometry
Cricetus
Membrane Glycoproteins
Mice, Inbred C3H
Pneumococcal Infections
Hormone Receptors, Cell Surface
Streptolysins
Macrophages, Peritoneal

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