TLR-4 pathway mediates the inflammatory response but not bacterial elimination in E. coli pneumonia

Janet S. Lee, Charles W. Frevert, Gustavo Matute-Bello, Mark M. Wurfel, Venus A. Wong, Shu Min Lin, John Ruzinski, Steve Mongovin, Richard B. Goodman, Thomas R. Martin

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

We examined the role of Toll-like receptor (TLR)-4 in modifying the lung inflammatory response and its effects on the bacterial recovery from the lungs following inhaled Escherichia coli in two different strains of TLR-4 mutant mice that are hyporesponsive to LPS. The C57BL/10ScN(tlr4lps-del) mice containing a deletion mutation in the TLR-4 gene showed lower proinflammatory cytokine levels, lower lung MPO activity, and less parenchymal and peribronchial inflammation compared with the C57BL/10ScSn mice, a related TLR-4 wild-type substrain. However, the C57BL/10ScN(tlr4lps-del) mutant showed lower bacterial recovery in the lungs following inhaled E. coli associated with a rapid but transient increase in air space neutrophil counts at 6 h. In comparison, the C3H/HeJ(tlr4Lps-d) mutant mice containing a Pro712His substitution in TLR-4 demonstrated lower proinflammatory cytokine levels, lower lung MPO activity, and lower neutrophil accumulation in the air spaces but showed no differences in the bacterial burden of inhaled E. coli at 6 h, when compared with the TLR-4 wild-type C3H/HeSnJ mice. Thus two different TLR-4 mutants showed attenuated inflammatory responses in the lungs, but the reduced inflammatory responses were not consistently associated with either improved or impaired bacterial elimination from the lungs. Our findings indicate that the inflammatory response to inhaled E. coli is TLR-4 dependent, but bacterial elimination depends on other factors in addition to TLR-4.

Original languageEnglish
Pages (from-to)L731-L738
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume289
Issue number5 33-5
DOIs
StatePublished - Nov 2005

Keywords

  • Bacterial proliferation
  • Escherichia coli
  • Lipopolysaccharide
  • Toll-like receptor-4

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