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Infection and Immunity, August 2009, p. 3170-3180, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00272-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mesenteric Lymph Nodes Confine Dendritic Cell-Mediated Dissemination of Salmonella enterica Serovar Typhimurium and Limit Systemic Disease in Mice{triangledown}

Sabrina Voedisch,1 Christian Koenecke,1 Sascha David,2 Heike Herbrand,1 Reinhold Förster,1 Mikael Rhen,3 and Oliver Pabst1*

Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany,1 Department of Nephrology, Hannover Medical School, 30625 Hannover, Germany,2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden3

Received 9 March 2009/ Returned for modification 13 April 2009/ Accepted 30 May 2009

In humans with typhoid fever or in mouse strains susceptible to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection, bacteria gain access to extraintestinal tissues, causing severe systemic disease. Here we show that in the gut-draining mesenteric lymph nodes (MLN), the majority of S. Typhimurium-carrying cells show dendritic-cell (DC) morphology and express the DC marker CD11c, indicating that S. Typhimurium bacteria are transported to the MLN by migratory DCs. In vivo FLT-3L-induced expansion of DCs, as well as stimulation of DC migration by Toll-like receptor agonists, results in increased numbers of S. Typhimurium bacteria reaching the MLN. Conversely, genetically impaired DC migration in chemokine receptor CCR7-deficient mice reduces the number of S. Typhimurium bacteria reaching the MLN. This indicates that transport of S. Typhimurium from the intestine into the MLN is limited by the number of migratory DCs carrying S. Typhimurium bacteria. In contrast, modulation of DC migration does not affect the number of S. Typhimurium bacteria reaching systemic tissues, indicating that DC-bound transport of S. Typhimurium does not substantially contribute to systemic S. Typhimurium infection. Surgical removal of the MLN results in increased numbers of S. Typhimurium bacteria reaching systemic sites early after infection, thereby rendering otherwise resistant mice susceptible to fatal systemic disease development. This suggests that the MLN provide a vital barrier shielding systemic compartments from DC-mediated dissemination of S. Typhimurium. Thus, confinement of S. Typhimurium in gut-associated lymphoid tissue and MLN delays massive extraintestinal dissemination and at the same time allows for the establishment of protective adaptive immune responses.

* Corresponding author. Mailing address: Institute of Immunology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. Phone: 49-511-5329725. Fax: 49-511-5329722. E-mail: Pabst.Oliver{at}MH-Hannover.de

{triangledown} Published ahead of print on 8 June 2009.

Editor: A. J. Bäumler

Infection and Immunity, August 2009, p. 3170-3180, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00272-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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