HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salazar-Gonzalez, R.-M. Articles by McSorley, S. J. Search for Related Content PubMed PubMed Citation Articles by Salazar-Gonzalez, R.-M. Articles by McSorley, S. J.

Salmonella Flagellin Induces Bystander Activation of Splenic Dendritic Cells and Hinders Bacterial Replication In Vivo¹

Rosa-Maria Salazar-Gonzalez^*, Aparna Srinivasan^*, Amanda Griffin^*, Guruprasaadh Muralimohan, James M. Ertelt^*, Rajesh Ravindran^*, Anthony T. Vella and Stephen J. McSorley^2,*

^* Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, McGuire Translational Research Facility, University of Minnesota Medical School, Minneapolis, MN 55455; and Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030

Bacterial flagellin is a target of innate and adaptive immune responses during Salmonella infection. Intravenous injection of Salmonella flagellin into C57BL/6 mice induced rapid IL-6 production and increased expression of activation markers by splenic dendritic cells. CD11b⁺, CD8⁺, and plasmacytoid dendritic cells each increased expression of CD86 and CD40 in response to flagellin stimulation, although CD11b⁺ dendritic cells were more sensitive than the other subsets. In addition, flagellin caused the rapid redistribution of dendritic cells from the red pulp and marginal zone of the spleen into the T cell area of the white pulp. Purified splenic dendritic cells did not respond directly to flagellin, indicating that flagellin-mediated activation of splenic dendritic cells occurs via bystander activation. IL-6 production, increased expression of activation markers, and dendritic cell redistribution in the spleen were dependent on MyD88 expression by bone marrow-derived cells. Avoiding this innate immune response to flagellin is important for bacterial survival, because Salmonella-overexpressing recombinant flagellin was highly attenuated in vivo. These data indicate that flagellin-mediated activation of dendritic cells is rapid, mediated by bystander activation, and highly deleterious to bacterial survival.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the National Institutes of Health AI056172 (to A.T.V. and S.J.M.).

² Address correspondence and reprint requests to Dr. Stephen J. McSorley, Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, McGuire Translational Research Facility, University of Minnesota Medical School, Minneapolis, MN 55455. E-mail address: mcsor002{at}umn.edu

³ Abbreviation used in this paper: Wt, wild type.

This article has been cited by other articles:

				J. T. Bates, S. Uematsu, S. Akira, and S. B. Mizel Direct Stimulation of tlr5+/+ CD11c+ Cells Is Necessary for the Adjuvant Activity of Flagellin J. Immunol., June 15, 2009; 182(12): 7539 - 7547. [Abstract] [Full Text] [PDF]

				C. J. Sanders, D. A. Moore III, I. R. Williams, and A. T. Gewirtz Both Radioresistant and Hemopoietic Cells Promote Innate and Adaptive Immune Responses to Flagellin J. Immunol., June 1, 2008; 180(11): 7184 - 7192. [Abstract] [Full Text] [PDF]