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Infection and Immunity, October 2009, p. 4480-4486, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00519-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of Nod1 in Mucosal Dendritic Cells during Salmonella Pathogenicity Island 1-Independent Salmonella enterica Serovar Typhimurium Infection {triangledown}

Lionel Le Bourhis,1 Joao Gamelas Magalhaes,1 Thirumahal Selvanantham,1 Leonardo H. Travassos,1 Kaoru Geddes,1 Jörg H. Fritz,1 Jérôme Viala,3 Karsten Tedin,4 Stephen E. Girardin,2 and Dana J. Philpott1*

Department of Immunology,1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada,2 Department of Paediatric Gastroenterology and Nutrition, Hôpital Robert Debré, 75935 Paris Cedex 19, France,3 Institut für Mikrobiologie und Tierseuchen, Freie Universität Berlin, Philippstrasse 13, D-10115 Berlin, Germany4

Received 11 May 2009/ Returned for modification 23 June 2009/ Accepted 10 July 2009

Recent advances in immunology have highlighted the critical function of pattern-recognition molecules (PRMs) in generating the innate immune response to effectively target pathogens. Nod1 and Nod2 are intracellular PRMs that detect peptidoglycan motifs from the cell walls of bacteria once they gain access to the cytosol. Salmonella enterica serovar Typhimurium is an enteric intracellular pathogen that causes a severe disease in the mouse model. This pathogen resides within vacuoles inside the cell, but the question of whether cytosolic PRMs such as Nod1 and Nod2 could have an impact on the course of S. Typhimurium infection in vivo has not been addressed. Here, we show that deficiency in the PRM Nod1, but not Nod2, resulted in increased susceptibility toward a mutant strain of S. Typhimurium that targets directly lamina propria dendritic cells (DCs) for its entry into the host. Using this bacterium and bone marrow chimeras, we uncovered a surprising role for Nod1 in myeloid cells controlling bacterial infection at the level of the intestinal lamina propria. Indeed, DCs deficient for Nod1 exhibited impaired clearance of the bacteria, both in vitro and in vivo, leading to increased organ colonization and decreased host survival after oral infection. Taken together, these findings demonstrate a key role for Nod1 in the host response to an enteric bacterial pathogen through the modulation of intestinal lamina propria DCs.

* Corresponding author. Mailing address: University of Toronto, Department of Immunology, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. Phone: (416) 978-7527. Fax: (416) 978-1938. E-mail: dana.philpott{at}utoronto.ca

{triangledown} Published ahead of print on 20 July 2009.

Editor: A. J. Bäumler

Infection and Immunity, October 2009, p. 4480-4486, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00519-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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