This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schurr, J. R.
Right arrow Articles by Kolls, J. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schurr, J. R.
Right arrow Articles by Kolls, J. K.

 Previous Article  |  Next Article 

Infection and Immunity, January 2005, p. 532-545, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.532-545.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Central Role of Toll-Like Receptor 4 Signaling and Host Defense in Experimental Pneumonia Caused by Gram-Negative Bacteria

Jill R. Schurr,1 Erana Young,1 Pat Byrne,1 Chad Steele,2 Judd E. Shellito,1 and Jay K. Kolls2*

Section of Pulmonary/Critical Care Medicine and the Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana,1 Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania2

Received 29 July 2004/ Returned for modification 7 September 2004/ Accepted 2 October 2004

Toll-like receptor 4 (TLR4) has been identified as a receptor for lipopolysaccharide. However, the precise role of TLR4 in regulating gene expression in response to an infection caused by gram-negative bacteria has not been fully elucidated. The role of TLR4 signaling in coordinating gene expression was assessed by gene expression profiling in lung tissue in a mouse model of experimental pneumonia with a low-dose infection of Klebsiella pneumoniae. We analyzed four mouse strains: C57BL/6 mice, which are resistant to bacterial dissemination; 129/SvJ mice, which are susceptible; C3H/HeJ mice, which are susceptible and have defective TLR4 signaling; and their respective control strain, C3H/HeN (intermediate resistance). At 4 h after infection, C57BL/6 and C3H/HeN mice demonstrated the greatest number of genes, with 67 shared induced genes which were TLR4 dependent and highly associated with the resistance phenotype. These genes included cytokine and chemokine genes required for neutrophil activation or recruitment, growth factor receptors, MyD88 (a critical adaptor protein for TLR signaling), and adhesion molecules. TLR4 signaling accounted for over 74% of the gene expression in the C3H background. These data suggest that early TLR4 signaling controls the vast majority of gene expression in the lung in response to an infection caused by gram-negative bacteria and that this subsequent gene expression determines survival of the host.

* Corresponding author. Mailing address: Children's Hospital of Pittsburgh, 3705 Fifth Ave., Suite 3765, Pittsburgh, PA 15213. Phone: (412) 692-5184. Fax: (412) 692-6645. E-mail: jay.kolls{at}chp.edu.

Editor: F. C. Fang

Infection and Immunity, January 2005, p. 532-545, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.532-545.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chan, Y. R., Liu, J. S., Pociask, D. A., Zheng, M., Mietzner, T. A., Berger, T., Mak, T. W., Clifton, M. C., Strong, R. K., Ray, P., Kolls, J. K. (2009). Lipocalin 2 Is Required for Pulmonary Host Defense against Klebsiella Infection. J. Immunol. 182: 4947-4956 [Abstract] [Full Text]  
  • Regueiro, V., Moranta, D., Campos, M. A., Margareto, J., Garmendia, J., Bengoechea, J. A. (2009). Klebsiella pneumoniae Increases the Levels of Toll-Like Receptors 2 and 4 in Human Airway Epithelial Cells. Infect. Immun. 77: 714-724 [Abstract] [Full Text]  
  • Craig, A., Mai, J., Cai, S., Jeyaseelan, S. (2009). Neutrophil Recruitment to the Lungs during Bacterial Pneumonia. Infect. Immun. 77: 568-575 [Full Text]  
  • Mizgerd, J. P., Skerrett, S. J. (2008). Animal models of human pneumonia. Am. J. Physiol. Lung Cell. Mol. Physiol. 294: L387-L398 [Abstract] [Full Text]  
  • Bhan, U., Lukacs, N. W., Osterholzer, J. J., Newstead, M. W., Zeng, X., Moore, T. A., McMillan, T. R., Krieg, A. M., Akira, S., Standiford, T. J. (2007). TLR9 Is Required for Protective Innate Immunity in Gram-Negative Bacterial Pneumonia: Role of Dendritic Cells. J. Immunol. 179: 3937-3946 [Abstract] [Full Text]  
  • Nelson, A. L., Ratner, A. J., Barasch, J., Weiser, J. N. (2007). Interleukin-8 Secretion in Response to Aferric Enterobactin Is Potentiated by Siderocalin. Infect. Immun. 75: 3160-3168 [Abstract] [Full Text]  
  • Jeyaseelan, S., Young, S. K., Fessler, M. B., Liu, Y., Malcolm, K. C., Yamamoto, M., Akira, S., Worthen, G. S. (2007). Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-beta (TRIF)-Mediated Signaling Contributes to Innate Immune Responses in the Lung during Escherichia coli Pneumonia. J. Immunol. 178: 3153-3160 [Abstract] [Full Text]  
  • Skerrett, S. J., Wilson, C. B., Liggitt, H. D., Hajjar, A. M. (2007). Redundant Toll-like receptor signaling in the pulmonary host response to Pseudomonas aeruginosa. Am. J. Physiol. Lung Cell. Mol. Physiol. 292: L312-L322 [Abstract] [Full Text]  
  • Berbee, J. F. P., van der Hoogt, C. C., Kleemann, R., Schippers, E. F., Kitchens, R. L., van Dissel, J. T., Bakker-Woudenberg, I. A. J. M., Havekes, L. M., Rensen, P. C. N. (2006). Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in Gram-negative sepsis. FASEB J. 20: 2162-2164 [Abstract] [Full Text]  
  • Jeyaseelan, S., Young, S. K., Yamamoto, M., Arndt, P. G., Akira, S., Kolls, J. K., Worthen, G. S. (2006). Toll/IL-1R Domain-Containing Adaptor Protein (TIRAP) Is a Critical Mediator of Antibacterial Defense in the Lung against Klebsiella pneumoniae but Not Pseudomonas aeruginosa. J. Immunol. 177: 538-547 [Abstract] [Full Text]  
  • Banus, H. A., Vandebriel, R. J., de Ruiter, H., Dormans, J. A. M. A., Nagelkerke, N. J., Mooi, F. R., Hoebee, B., van Kranen, H. J., Kimman, T. G. (2006). Host Genetics of Bordetella pertussis Infection in Mice: Significance of Toll-Like Receptor 4 in Genetic Susceptibility and Pathobiology.. Infect. Immun. 74: 2596-2605 [Abstract] [Full Text]  
  • Regueiro, V., Campos, M. A., Pons, J., Alberti, S., Bengoechea, J. A. (2006). The uptake of a Klebsiella pneumoniae capsule polysaccharide mutant triggers an inflammatory response by human airway epithelial cells. Microbiology 152: 555-566 [Abstract] [Full Text]  
  • Mann, P. B., Wolfe, D., Latz, E., Golenbock, D., Preston, A., Harvill, E. T. (2005). Comparative Toll-Like Receptor 4-Mediated Innate Host Defense to Bordetella Infection. Infect. Immun. 73: 8144-8152 [Abstract] [Full Text]  
  • Martin, T. R., Frevert, C. W. (2005). Innate Immunity in the Lungs. Proc Am Thorac Soc 2: 403-411 [Abstract] [Full Text]  
  • Jeyaseelan, S., Manzer, R., Young, S. K., Yamamoto, M., Akira, S., Mason, R. J., Worthen, G. S. (2005). Induction of CXCL5 During Inflammation in the Rodent Lung Involves Activation of Alveolar Epithelium. Am. J. Respir. Cell Mol. Bio. 32: 531-539 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»