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Infection and Immunity, February 2004, p. 788-794, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.788-794.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Role of Toll-Like Receptor 4 in Gram-Positive and Gram-Negative Pneumonia in Mice

Judith Branger,1,2* Sylvia Knapp,1 Sebastiaan Weijer,1 Jaklien C. Leemans,1 Jennie M. Pater,1 Peter Speelman,2 Sandrine Florquin,3 and Tom van der Poll1,2

Laboratory of Experimental Internal Medicine,1 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS,2 Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands3

Received 30 June 2003/ Returned for modification 2 September 2003/ Accepted 3 November 2003

To determine the role of Toll-like receptor 4 (TLR4) in the immune response to pneumonia, C3H/HeJ mice (which display a mutant nonfunctional TLR4) and C3H/HeN wild-type mice were intranasally infected with either Streptococcus pneumoniae (a common gram-positive respiratory pathogen) or Klebsiella pneumoniae (a common gram-negative respiratory pathogen). In cases of pneumococcal pneumonia, TLR4 mutant mice showed a reduced survival only after infection with low-level bacterial doses, which was associated with a higher bacterial burden in their lungs 48 h postinfection. In Klebsiella pneumonia, TLR4 mutant mice demonstrated a shortened survival after infection with either a low- or a high-level bacterial dose together with an enhanced bacterial outgrowth in their lungs. These data suggest that TLR4 contributes to a protective immune response in both pneumococcal and Klebsiella pneumonia and that its role is more important in respiratory tract infection caused by the latter (gram-negative) pathogen.

* Corresponding author. Mailing address: Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Room G2-132, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-566 9111. Fax: 31-20-697 7192. E-mail: j.branger{at}amc.uva.nl.

Editor: F. C. Fang

Infection and Immunity, February 2004, p. 788-794, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.788-794.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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