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

Publication ,  Journal Article
St John, AL; Ang, WXG; Huang, M-N; Kunder, CA; Chan, EW; Gunn, MD; Abraham, SN
Published in: Immunity
September 18, 2014

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.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

September 18, 2014

Volume

41

Issue

3

Start / End Page

440 / 450

Location

United States

Related Subject Headings

  • Yersinia pestis
  • Thiophenes
  • Sphingosine
  • Receptors, Lysosphingolipid
  • Receptors, CCR7
  • Receptors, CCR2
  • Propylene Glycols
  • Plague
  • Phagocytes
  • Oxadiazoles
 

Citation

APA
Chicago
ICMJE
MLA
NLM
St John, A. L., Ang, W. X. G., Huang, M.-N., Kunder, C. A., Chan, E. W., Gunn, M. D., & Abraham, S. N. (2014). S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection. Immunity, 41(3), 440–450. https://doi.org/10.1016/j.immuni.2014.07.013
St John, Ashley L., WX Gladys Ang, Min-Nung Huang, Christian A. Kunder, Elizabeth W. Chan, Michael D. Gunn, and Soman N. Abraham. “S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection.Immunity 41, no. 3 (September 18, 2014): 440–50. https://doi.org/10.1016/j.immuni.2014.07.013.
St John AL, Ang WXG, Huang M-N, Kunder CA, Chan EW, Gunn MD, et al. S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection. Immunity. 2014 Sep 18;41(3):440–50.
St John, Ashley L., et al. “S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection.Immunity, vol. 41, no. 3, Sept. 2014, pp. 440–50. Pubmed, doi:10.1016/j.immuni.2014.07.013.
St John AL, Ang WXG, Huang M-N, Kunder CA, Chan EW, Gunn MD, Abraham SN. S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection. Immunity. 2014 Sep 18;41(3):440–450.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

September 18, 2014

Volume

41

Issue

3

Start / End Page

440 / 450

Location

United States

Related Subject Headings

  • Yersinia pestis
  • Thiophenes
  • Sphingosine
  • Receptors, Lysosphingolipid
  • Receptors, CCR7
  • Receptors, CCR2
  • Propylene Glycols
  • Plague
  • Phagocytes
  • Oxadiazoles