S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection.

Published

Journal Article

Pathologically swollen lymph nodes (LNs), or buboes, characterize Yersinia pestis infection, yet how they form and function is unknown. We report that colonization of the draining LN (dLN) occurred due to trafficking of infected dendritic cells and monocytes in temporally distinct waves in response to redundant chemotactic signals, including through CCR7, CCR2, and sphingosine-1-phospate (S1P) receptors. Retention of multiple subsets of phagocytes within peripheral LNs using the S1P receptor agonist FTY720 or S1P1-specific agonist SEW2871 increased survival, reduced colonization of downstream LNs, and limited progression to transmission-associated septicemic or pneumonic disease states. Conditional deletion of S1P1 in mononuclear phagocytes abolished node-to-node trafficking of infected cells. Thus, Y. pestis-orchestrated LN remodeling promoted its dissemination via host cells through the lymphatic system but can be blocked by prevention of leukocyte egress from DLNs. These findings define a novel trafficking route of mononuclear phagocytes and identify S1P as a therapeutic target during infection.

Full Text

Duke Authors

Cited Authors

  • St John, AL; Ang, WXG; Huang, M-N; Kunder, CA; Chan, EW; Gunn, MD; Abraham, SN

Published Date

  • September 2014

Published In

Volume / Issue

  • 41 / 3

Start / End Page

  • 440 - 450

PubMed ID

  • 25238098

Pubmed Central ID

  • 25238098

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2014.07.013

Language

  • eng