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 Google Scholar
Google Scholar
Right arrow Articles by Puliti, M.
Right arrow Articles by Tissi, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Puliti, M.
Right arrow Articles by Tissi, L.

 Previous Article  |  Next Article 

Infection and Immunity, April 2009, p. 1524-1531, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.00965-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Toll-Like Receptor 2 Deficiency Is Associated with Enhanced Severity of Group B Streptococcal Disease {triangledown}

Manuela Puliti,1 Satoshi Uematsu,2 Shizuo Akira,2 Francesco Bistoni,1 and Luciana Tissi1*

Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy,1 Department of Host Defence Research Institute for Microbial Diseases Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan2

Received 1 August 2008/ Returned for modification 6 October 2008/ Accepted 19 January 2009

Group B streptococcus (GBS) has been recognized as an ever-growing cause of serious invasive infections in nonpregnant adults, in particular, in association with severe underlying diseases. The most common manifestations include primary bacteremia, urinary tract infections, pneumonia, meningitis, peritonitis, and osteoarticular infections. Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacteria. TLR2 function was investigated in murine GBS-induced sepsis and arthritis in wild-type (wt) and TLR2-deficient (TLR2–/–) mice. Mice were infected with different doses of GBS (107, 5 x 106, or 106 CFU per mouse). Mortality, appearance of arthritis, GBS growth in the organs, and local and systemic cytokine and chemokine production were examined. TLR2–/– mice showed earlier and higher mortality rates and increased incidence and severity of arthritis than wt mice at all the infecting doses employed. Histopathological analysis of the joints confirmed clinical observations. TLR2–/– mice exhibited a higher microbial load in blood, kidneys, and joints than wt animals. In vitro experiments performed with peritoneal polymorphonuclear cells and macrophages showed a significantly lower bactericidal ability of cells from TLR2–/– mice. Increased systemic and local levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein-1{alpha} (MIP-1{alpha}), and MIP-2 accompanied the more severe development of sepsis and arthritis in TLR2–/– mice. In conclusion, the lack of TLR2 was associated with an impaired host resistance to GBS infection, likely due to a diminished bacterial clearing and a consequent enhanced inflammatory response.

* Corresponding author. Mailing address: Department of Experimental Medicine and Biochemical Sciences, Microbiology Section, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Phone: 39 075 585 7409. Fax: 39 075 585 7400. E-mail: tissi{at}unipg.it

{triangledown} Published ahead of print on 29 January 2009.

Editor: B. A. McCormick

Infection and Immunity, April 2009, p. 1524-1531, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.00965-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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