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Infection and Immunity, November 2008, p. 5421-5428, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00615-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Important Role for Toll-Like Receptor 9 in Host Defense against Meningococcal Sepsis{triangledown}

Hong Sjölinder,1*,{dagger} Trine H. Mogensen,2*,{dagger} Mogens Kilian,3 Ann-Beth Jonsson,1,{ddagger} and Søren R. Paludan3,{ddagger}

Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden,1 Department of Infectious Diseases, Skejby Hospital-Aarhus University Hospital, DK-8200, Aarhus N, Denmark,2 Institute of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus C, Denmark3

Received 21 May 2008/ Returned for modification 2 July 2008/ Accepted 3 September 2008

Neisseria meningitidis is a leading cause of meningitis and sepsis. The pathogenesis of meningococcal disease is determined by both bacterial virulence factors and the host inflammatory response. Toll-like receptors (TLRs) are prominent activators of the inflammatory response, and TLR2, -4, and -9 have been reported to be involved in the host response to N. meningitidis. While TLR4 has been suggested to play an important role in early containment of infection, the roles of TLR2 and TLR9 in meningococcal disease are not well described. Using a model for meningococcal sepsis, we report that TLR9–/– mice displayed reduced survival and elevated levels of bacteremia compared to wild-type mice. In contrast, TLR2–/– mice controlled the infection in a manner comparable to that of wild-type mice. TLR9 deficiency was also associated with reduced bactericidal activity in vitro, which was accompanied by reduced production of nitric oxide by TLR9-deficient macrophages. Interestingly, TLR9–/– mice recruited more macrophages to the bloodstream than wild-type mice and produced elevated levels of cytokines at late time points during infection. At the cellular level, activation of signal transduction and induction of cytokine gene expression were independent of TLR2 or TLR9 in macrophages and conventional dendritic cells. In contrast, plasmacytoid dendritic cells relied entirely on TLR9 to induce these activities. Thus, our data demonstrate an important role for TLR9 in host defense against N. meningitidis.

* Corresponding author. Mailing address for Hong Sjölinder: Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, P.O. Box 582, Uppsala, Sweden. Phone: 46 18 471 46 05. Fax: 46 18 50 98 76. E-mail: hong.sjolinder{at}imbim.uu.se. Mailing address for Trine H. Mogensen: Department of Infectious Diseases, Skejby Hospital, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. Phone: 45 89498499. Fax: 45 89498310. E-mail: trine.mogensen{at}dadlnet.dk

{triangledown} Published ahead of print on 15 September 2008.

Editor: J. N. Weiser

{dagger} These two authors contributed equally to this work.

{ddagger} These two authors contributed equally to this work.

Infection and Immunity, November 2008, p. 5421-5428, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00615-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mogensen, T. H. (2009). Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clin. Microbiol. Rev. 22: 240-273 [Abstract] [Full Text]  


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