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S1P-Dependent Trafficking of Intracellular Yersinia pestis through Lymph Nodes Establishes Buboes and Systemic Infection IMMUNITY St John, A. L., Ang, W., Huang, M., Kunder, C. A., Chan, E. W., Gunn, M. D., Abraham, S. N. 2014; 41 (3): 440-450

Abstract

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.

View details for DOI 10.1016/j.immuni.2014.07.013

View details for Web of Science ID 000342626500014

View details for PubMedID 25238098

View details for PubMedCentralID PMC4440548