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Streptococcus mitis cell walls and lipopolysaccharide induce lethality in D-galactosamine-sensitized mice by a tumor

D Le Roy1, P Morand, S Lengacher

  • 1Department of Medicine, CHUV-Lausanne, Switzerland.

Insights

Purified cell walls from Streptococcus mitis triggered tumor necrosis factor and caused lethal shock in mice, similar to lipopolysaccharide (LPS). Anti-tumor necrosis factor antibodies protected against this effect.

Area of Science:

  • Immunology
  • Microbiology
  • Pathology

Background:

  • Lipopolysaccharide (LPS) from Gram-negative bacteria is a potent inducer of inflammatory responses.
  • The role of Gram-positive bacterial components in inducing similar inflammatory responses requires further investigation.

Purpose of the Study:

  • To investigate the in vitro and in vivo effects of purified cell walls from Streptococcus mitis.
  • To compare the inflammatory and toxic effects of Gram-positive cell walls with LPS.

Main Methods:

  • Incubation of whole blood from LPS-sensitive and LPS-resistant mice with purified Streptococcus mitis cell walls.
  • Administration of Streptococcus mitis cell walls or LPS to D-galactosamine-sensitized mice.
  • Assessment of lethality and histopathophysiological changes.
  • Evaluation of the effect of anti-tumor necrosis factor antibodies.

Main Results:

  • Streptococcus mitis cell walls induced tumor necrosis factor (TNF) in vitro in whole blood from both LPS-sensitive and LPS-resistant mice.
  • Purified cell walls were as effective as heat-killed bacteria in causing lethal shock in D-galactosamine-sensitized mice.
  • Anti-TNF antibodies significantly suppressed the lethality induced by cell walls.
  • Histopathological findings were indistinguishable between mice challenged with LPS and those challenged with Gram-positive cell walls.

Conclusions:

  • Purified cell walls of Streptococcus mitis are potent inducers of TNF and lethal shock.
  • The toxic effects of Gram-positive cell walls are mediated by TNF, similar to LPS.
  • Gram-positive bacterial components can elicit responses comparable to LPS, impacting host defense and pathology.

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