Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines.

Published

Journal Article

We report that infection of draining lymph nodes (DLNs) by Salmonella typhimurium results in the specific downregulation of the homeostatic chemokines CCL21 and CXCL13, which are essential for normal DLN organization and function. Our data reveal that the mechanism of this suppression is dependent on S. typhimurium LPS (sLPS). The decrease in CCL21 expression involves interaction between sLPS and CCL21-producing cells within DLNs, triggering a distinct Toll-like receptor 4 (TLR4)-mediated host signaling response. In this response, suppressor of cytokine signaling-3 (Socs3) is upregulated, which negatively regulates mothers against decapentaplegic homolog-3 (Smad3)-initiated production of CCL21. Disruption of lymph node architecture and cellular trafficking enhances S. typhimurium virulence and could represent a mechanism of immune suppression used by pathogens that primarily target lymphoid tissue.

Full Text

Duke Authors

Cited Authors

  • St John, AL; Abraham, SN

Published Date

  • November 2009

Published In

Volume / Issue

  • 15 / 11

Start / End Page

  • 1259 - 1265

PubMed ID

  • 19855398

Pubmed Central ID

  • 19855398

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/nm.2036

Language

  • eng

Conference Location

  • United States