YopM and Plague
YopM is required for full virulence of Yersinia pestis in systemic and bubonic plague, where it functions to counteract innate defenses. Our lab has been using the systemic plague model to identify the immunologic steps at which YopM has its earliest effects and then to work back to the associated signaling pathways affected by YopM. We have found that Gr1+ cells (polymorphonuclear leukocytes (PMNs), monocytes, and some dendritic cells (DCs)) are required to limit the growth of YopM− Y. pestis. Further, when mice lack the chemokine receptor CCR2, YopM− Y. pestis grows as well as the parent strain in both systemic and bubonic plague, indicating that YopM’s molecular targets ultimately act through CCR2. YopM disables the recruitment of CCR2+ Gr1+ inflammatory DCs into spleen, whereas in liver, it is the function of CCR2+ Gr1+ PMNs that is undermined. Microarray analysis of transcriptional differences in CD11b+ cells from spleens of mice infected with parent vs. YopM− Y. pestis points to the downregulation of expression of the transcription factor Egr-1 and of a chemokine ligand for CCR2, CCL2, as effects of YopM initiated by 1 h after infection. These findings provide a link between YopM’s effects at the molecular and immunological levels.
KeywordsYersinia Enterocolitica Yersinia Pestis Growth Deficit Iron Acquisition System Pneumonic Plague
This study was supported by US Public Health Service (NIAID) Grant AI067869. The new data about the microarray study involved contributions of effort from Annette M Uittenbogaard VMT, Tanya Myers-Morales MS, Amanda A Gorman MS, Zhan Ye PhD, Donald A Cohen PhD, and Alan M Kaplan PhD (all of the Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY, USA). Jenny P.-Y. Ting PhD designed the custom mouse oligonucleotide array used in the study, and W June Brickey PhD performed the hybridizations and their analysis (both of the Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, North Carolina USA).
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