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1 August 2007

Volume 196, Number 3
The Journal of Infectious Diseases 2007;196:475–484
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19603-0019$15.00
DOI: 10.1086/518893
MAJOR ARTICLE

Reduced Toll‐Like Receptor 4 Expression in Children with Asymptomatic Bacteriuria

Bryndís Ragnarsdóttir,1

Martin Samuelsson,1

Mattias C. U. Gustafsson,1

Irene Leijonhufvud,1

Diana Karpman,2 and

Catharina Svanborg1

1Department of Microbiology, Immunology, and Glycobiology, Institute of Laboratory Medicine, and 2Department of Pediatrics, Lund University, Lund, Sweden

Toll‐like receptor (TLR) 4 is essential for the defense against infection with gram‐negative pathogens, but reduced TLR4 expression has not been linked to altered disease susceptibility in humans. In mice, Tlr4 controls the mucosal response to Escherichia coli urinary tract infections. Inactivation of mouse Tlr4 causes an asymptomatic carrier state resembling asymptomatic bacteriuria (ABU). The present study compared neutrophil TLR4 expression levels between children with ABU ( ) and age‐matched control subjects ( ), and significantly lower levels were detected in the patients with ABU. We also found elevated levels of the TLR4 adaptor protein TRIF and reduced levels of the TLR4‐inhibitor SIGIRR in the patients with ABU, but MyD88 and TRAM levels were not significantly altered. Altered TLR4 and adaptor protein expression might impair TLR4 signaling and explain the weak mucosal response to urinary tract infection in patients who develop ABU rather than symptomatic disease.

Received 25 September 2006; accepted 14 February 2007; electronically published 21 June 2007.

Reprints or correspondence: Dr. Catharina Svanborg, Dept. of Microbiology, Immunology, and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, 22362 Lund, Sweden ().

Cited by

Willem Joost Wiersinga, Cornelis van’t Veer, Petra S. van den Pangaart, Arjen M. Dondorp, Nicholas P. Day, Sharon J. Peacock, Tom van der Poll. (2009) Immunosuppression associated with interleukin-1R-associated-kinase-M upregulation predicts mortality in Gram-negative sepsis (melioidosis). Critical Care Medicine 37:2, 569-576
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Abstract-Full Text-PDF Version (184 kB)
B. Ragnarsdóttir, H. Fischer, G. Godaly, J. Grönberg-Hernandez, M. Gustafsson, D. Karpman, A. C. Lundstedt, N. Lutay, S. Rämisch, M. L. Svensson, B. Wullt, M. Yadav, C. Svanborg. (2008) TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections. European Journal of Clinical Investigation 38, 12-20
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J. Song, S. N. Abraham. (2008) Innate and adaptive immune responses in the urinary tract. European Journal of Clinical Investigation 38, 21-28
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  • Potential conflicts of interest: none reported.

    Presented in part: TOLL 2006: Recent Advances in Pattern Recognition, Salvador, Brazil, 4–7 March 2006 (poster 151).

    Financial support: This study was supported by grants from the Swedish Medical Research Council; the Royal Physiographic Society; the Medical Faculty, Lund University; the Network of Excellence Europathogenomics; the Swedish Cancer Society; and the Crafoord, Österlund, Lundberg, Lundgren, Maggie Stephens, Söderberg, H. J. Forssman, J&A Persson, and Wallenberg Foundations. C.S. was a recipient of a Bristol‐Myers Squibb unrestricted grant.

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