Modulation of adherence, invasion, and tumor necrosis factor alpha secretion during the early stages of infection by Streptococcus pneumoniae ClpL

Nhat Tu Le, Hye Yoon Jeong, Hyog Young Kwon, Abiodun D. Ogunniyi, James C. Paton, Suhk Neung Pyo, Dong Kwon Rhee

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Heat shock proteins (HSPs) play a pivotal role as chaperones in the folding of native and denatured proteins and can help pathogens penetrate host defenses. However, the underlying mechanism(s) of modulation of virulence by HSPs has not been fully determined. In this study, the role of the chaperone ClpL in the pathogenicity of Streptococcus pneumoniae was assessed. A clpL mutant adhered to and invaded nasopharyngeal or lung cells much more efficiently than the wild type adhered to and invaded these cells in vitro, as well as in vivo, although it produced the same amount of capsular polysaccharide. However, the level of secretion of tumor necrosis factor alpha (TNF-α) from macrophages infected with the clpL mutant was significantly lower than the level of secretion elicited by the wild type during the early stages of infection. Interestingly, treatment of the human lung epithelial carcinoma A549 and murine macrophage RAW 264.7 cell lines with cytochalasin D, an inhibitor of actin polymerization, increased adherence of the mutant to the host cells. In contrast, cytochalasin D treatment of RAW 264.7 cells decreased TNF-α secretion after infection with either the wild type or the mutant. However, pretreatment of cell lines with the actin polymerization activator jasplakinolide reversed these phenotypes. These findings indicate, for the first time, that the ClpL chaperone represses adherence of S. pneumoniae to host cells and induces secretion of TNF-α via a mechanism dependent upon actin polymerization during the initial infection stage.

Original languageEnglish (US)
Pages (from-to)2996-3005
Number of pages10
JournalInfection and Immunity
Volume75
Issue number6
DOIs
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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