Lethal Escherichia coli and Salmonella typhimurium endotoxemia is mediatedthrough different pathways

Citation
Mg. Netea et al., Lethal Escherichia coli and Salmonella typhimurium endotoxemia is mediatedthrough different pathways, EUR J IMMUN, 31(9), 2001, pp. 2529-2538
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
0014-2980 → ACNP
Volume
31
Issue
9
Year of publication
2001
Pages
2529 - 2538
Database
ISI
SICI code
0014-2980(200109)31:9<2529:LECAST>2.0.ZU;2-K
Abstract
Despite the differences in the molecular structure between lipopolysacchari des (LPS) isolated from Escherichia coli, Klebsiella pneumoniae or Salmonel la typhimurium, the potential differences in their biological effects in vi vo have not been investigated. In the present study, TNF and LT double knoc k-out (TNF-/-LT-/-) mice were almost as susceptible as TNF+/+LT+/+ controls to S. typhimurium LPS, but they were significantly more resistant to letha l endotoxemia induced by E. coli or K. pneumoniae LPS. The effect was not d ue to endotoxin-associated proteins. In the knock-out mice, this difference in lethality was accompanied by decreased interleukin-1 (IL-1) and interfe ron-gamma (IFN-gamma) production after challenge with E. coli LIPS, whereas after S. typhimurium LPS more IL-1 and IFN-gamma were produced. In contras t, more IL-10 was produced after challenge of mice with E. coli LIPS than w ith S. typhymurium LPS. The hypothesis that a combination of pro-inflammato ry cytokines is responsible for the mortality after S. typhimurium LPS was suggested by experiments in mice deficient in IL-1 beta -converting enzyme (ICE-/- mice). ICE-/- mice, lacking mature IL-1 beta and IL-18, but also de fective in IFN-gamma and TNF production, were completely protected against both E. coli and S. typhimurium LPS. Experiments in Toll-like receptor (TLR )-4 defective mice suggested that the difference is not due to differential activation of TLR4. In conclusion, TNF and LT play a central role in the l ethality due to E. coli LPS, whereas the lethal effects of S. typhimurium L PS are mediated through mechanisms also involving other cytokines. such as IFN-gamma, IL-1 and IL-18.