Skip to main content
Article thumbnail
Location of Repository

Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice

By Mark C. Dessing, Robert A. Hirst, Alex F. de Vos and Tom van der Poll

Abstract

Background: Pneumolysin (PLN) is an intracellular toxin of Streptococcus pneumoniae that has been implicated as a major virulence factor in infections caused by this pathogen. Conserved bacterial motifs are recognized by the immune system by pattern recognition receptors among which the family of Toll-like receptors (TLRs) prominently features. The primary objective of the present study was to determine the role of TLR2 and TLR4 in lung inflammation induced by intrapulmonary delivery of PLN.\ud Methodology/Results: First, we confirmed that purified PLN activates cells via TLR4 (not via TLR2) in vitro, using human embryonic kidney cells transfected with either TLR2 or TLR4. Intranasal administration of PLN induced an inflammatory response in the pulmonary compartment of mice in vivo, as reflected by influx of neutrophils, release of proinflammatory cytokines and chemokines, and a rise in total protein concentrations in bronchoalveolar lavage fluid. These PLN-induced responses were dependent in part, not only on TLR4, but also on TLR2, as indicated by studies using TLR deficient mice.\ud Conclusion: These data suggest that although purified PLN is recognized by TLR4 in vitro, PLN elicits lung inflammation in vivo by mechanisms that may involve multiple TLRs

Publisher: Public Library of Science
Year: 2009
DOI identifier: 10.1371/journal.pone.0007993
OAI identifier: oai:lra.le.ac.uk:2381/8848
Journal:

Suggested articles

Citations

  1. (1998). Amino acid changes affecting the activity of pneumolysin alter the behaviour of pneumococci in pneumonia. doi
  2. Biol Rev 65: 187–207, first page, table of contents.
  3. (2009). Camilli A
  4. (1977). Cellular location of pneumolysin. doi
  5. (2006). Comparison of lipoteichoic acid from different serotypes of Streptococcus pneumoniae. doi
  6. (1999). Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.
  7. (1997). Differences in virulence for mice among Streptococcus pneumoniae strains of capsular types
  8. (1999). Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. doi
  9. (1992). Effect of insertional inactivation of the genes encoding pneumolysin and autolysin on the virulence of Streptococcus pneumoniae type 3. doi
  10. (2004). Endogenous ligands of Toll-like receptors. doi
  11. (1989). Expression of the pneumolysin gene in Escherichia coli: rapid purification and biological properties. doi
  12. (1983). Ferrante A
  13. (1998). Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. doi
  14. (2002). Induction of cytokine production in human T cells and monocytes by highly purified lipoteichoic acid: involvement of Toll-like receptors and CD14.
  15. (2002). Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction. doi
  16. (2003). Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharidebinding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. doi
  17. (2001). Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling. doi
  18. (2006). Pathogen recognition and innate immunity. doi
  19. (1999). Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by tolllike receptor 2. doi
  20. (2003). Pneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating Toll-like receptor 2. doi
  21. (2002). Pneumolysin activates the synthesis and release of interleukin-8 by human neutrophils in vitro. doi
  22. (1991). Pneumolysin induces the salient histologic features of pneumococcal infection in the rat lung in vivo. doi
  23. (1994). Pneumolysin stimulates production of tumor necrosis factor alpha and interleukin-1 beta by human mononuclear phagocytes.
  24. (2004). Pneumolysin-induced lung injury is independent of leukocyte trafficking into the alveolar space. doi
  25. (1987). Production and purification of Streptococcus pneumoniae hemolysin (pneumolysin).
  26. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. doi
  27. (2003). Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. doi
  28. (1989). Reduced virulence of a defined pneumolysin-negative mutant of Streptococcus pneumoniae.
  29. (2005). Regulation of lung injury and repair by Toll-like receptors and hyaluronan. doi
  30. (2006). Role of pneumolysin for the development of acute lung injury in pneumococcal pneumonia. doi
  31. (2002). Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice. doi
  32. (2008). Role played by Toll-like receptors 2 and 4 in lipoteichoic acid-induced lung inflammation and coagulation. doi
  33. (2002). Roles of interleukin-6 and macrophage inflammatory protein-2 in pneumolysin-induced lung inflammation in mice. doi
  34. (2001). Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Tolllike receptor 4. doi
  35. (2005). Structural basis of pore formation by the bacterial toxin pneumolysin. doi
  36. (2001). Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus. doi
  37. (1996). The contribution of pneumolysin to the pathogenicity of Streptococcus pneumoniae. doi
  38. (1990). The effect of Streptococcus pneumoniae pneumolysin on human respiratory epithelium in vitro. doi
  39. (2004). The role of pneumolysin in pneumococcal pneumonia and meningitis. doi
  40. (2007). Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.