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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.
Abstract:
YopM, a protein toxin of Yersinia pestis, is necessary for virulence in a mouse model of systemic plague. We previously reported YopM-dependent natural killer (NK) cell depletion from blood and spleen samples of infected mice. However, in this study we found that infection with Y. pestis KIM5 (YopM(+)) caused depletion of NK cells in the spleen, but not in the liver, and antibody-mediated ablation of NK cells had no effect on bacterial growth. There was no YopM-associated effect on the percentage of dendritic cells (DCs) or polymorphonuclear leukocytes (PMNs) in the early stage of infection; however, there was a YopM-associated effect on PMN integrity and on the influx of monocytes into the spleen. Ablation of Gr1(+) cells caused loss of the growth defect of YopM(-) Y. pestis in both the liver and spleen. In contrast, ablation of macrophages/DCs inhibited growth of both parent and mutant bacteria, accompanied by significantly fewer lesion sites in the liver. These results point toward PMNs and inflammatory monocytes as major cell types that control growth of YopM(-) Y. pestis. Infection with fully virulent Y. pestis CO92 and a YopM(-) derivative by intradermal and intranasal routes showed that the absence of YopM significantly increased the 50% lethal dose only in the intradermal model, suggesting a role for YopM in bubonic plague, in which acute inflammation occurs soon after infection.
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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