Distinct CCR2(+) Gr1(+) Cells Control Growth of the Yersinia pestis Delta yopM Mutant in Liver and Spleen during Systemic Plague

作者：Ye Zhan; Uittenbogaard Annette M; Cohen Donald A; Kaplan Alan M; Ambati Jayakrishna; Straley Susan C^*

来源：Infection and Immunity, 2011, 79(2): 674-687.

DOI：10.1128/IAI.00808-10

We are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein YopM of the plague bacterium Yersinia pestis. In this study, we pursued previous findings that Gr1(+) cells are required to selectively limit growth of Delta yopM Y. pestis and that CD11b(+) cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parent Y. pestis. When PMNs were ablated from mice, Delta yopM Y. pestis grew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to Delta yopM Y. pestis in both organs. In spleen, the Gr1(+) cells differentially recruited by parent and Delta yopM Y. pestis infections were CCR2(+) Gr1(+) CD11b(+) CD11c(Lo-Int) MAC3(+) iNOS(+) (inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the Delta yopM mutant was relieved by the parent Y. pestis strain in a coinfection assay in which the parent strain could affect the fate of the mutant in trans. In a mouse model of bubonic plague, CCR2 also was shown to be required for Delta yopM Y. pestis to show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.

• 出版日期2011-2