Article abstract
Nature Medicine 15, 1259 - 1265 (2009)
Published online: 25 October 2009 | doi:10.1038/nm.2036
Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines
Ashley L St John1 & Soman N Abraham1,2,3,4
Abstract
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.
- Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
- Departments of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
- Program in Emerging Infectious Diseases, Duke-National University of Singapore, Graduate Medical School, Singapore, USA.
Correspondence to: Soman N Abraham1,2,3,4 e-mail: soman.abraham@duke.edu
