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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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Copyright © 2004 by the American Society for Microbiology. All rights reserved.