Gr1+ cells control growth of YopM-negative yersinia pestis during systemic plague

Zhan Ye1, Edward J Kerschen, Donald A Cohen

  • 1Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536-0298, USA.

Insights

Yersinia pestis YopM toxin impacts immune cell responses during plague. YopM influences polymorphonuclear leukocytes and monocytes, crucial for controlling YopM-deficient bacterial growth, particularly in bubonic plague models.

Area of Science:

  • Immunology
  • Microbiology
  • Pathogenesis

Background:

  • Yersinia pestis YopM is a virulence factor in systemic plague.
  • Previous studies indicated YopM depletes natural killer (NK) cells.

Purpose of the Study:

  • Investigate YopM's role in immune cell modulation during Y. pestis infection.
  • Determine the impact of YopM on NK cells, dendritic cells (DCs), and polymorphonuclear leukocytes (PMNs).
  • Identify immune cells critical for controlling YopM-deficient Y. pestis growth.

Main Methods:

  • Infection of mice with Y. pestis strains (YopM+ and YopM-).
  • Analysis of immune cell populations (NK cells, DCs, PMNs, monocytes) in spleen and liver.
  • Antibody-mediated depletion of specific immune cell types (NK cells, Gr1+ cells, macrophages/DCs).
  • Assessment of bacterial growth and lesion formation.
  • Determination of 50% lethal dose (LD50) via intradermal and intranasal routes.

Main Results:

  • YopM-expressing Y. pestis depleted NK cells in the spleen but not the liver; NK cell ablation did not affect bacterial growth.
  • YopM affected PMN integrity and monocyte influx into the spleen.
  • Depletion of Gr1+ cells abrogated the growth defect of YopM-deficient Y. pestis.
  • Depletion of macrophages/DCs inhibited growth of both Y. pestis strains and reduced liver lesions.
  • Absence of YopM significantly increased the LD50 only in the intradermal plague model.

Conclusions:

  • PMNs and inflammatory monocytes are key in controlling YopM-deficient Y. pestis growth.
  • YopM plays a role in Y. pestis pathogenesis, particularly in the context of acute inflammation seen in bubonic plague.

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