Early Apoptosis of Macrophages Modulated by Injection of Yersinia pestis YopK Promotes Progression of Primary Pneumonic Plague

PLoS Pathogens

Kristen N. Peters¹  Jennifer M. Hughes Hanks¹  Deborah M. Anderson¹  Charles R. Brown²  Miqdad O. Dhariwala² 

[1] Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America;Laboratory for Infectious Disease Research, University of Missouri, Columbia, Missouri, United States of America

关键词: Yersinia pestis;    Macrophages;    Apoptosis;    Inflammation;    Alveolar macrophages;    Cytokines;    Pneumonic plagues;    Respiratory infections;   

DOI  :  10.1371/journal.ppat.1003324

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Yersinia pestis causes pneumonic plague, a disease characterized by inflammation, necrosis and rapid bacterial growth which together cause acute lung congestion and lethality. The bacterial type III secretion system (T3SS) injects 7 effector proteins into host cells and their combined activities are necessary to establish infection. Y. pestis infection of the lungs proceeds as a biphasic inflammatory response believed to be regulated through the control of apoptosis and pyroptosis by a single, well-conserved T3SS effector protein YopJ. Recently, YopJ-mediated pyroptosis, which proceeds via the NLRP3-inflammasome, was shown to be regulated by a second T3SS effector protein YopK in the related strain Y. pseudotuberculosis. In this work, we show that for Y. pestis, YopK appears to regulate YopJ-mediated apoptosis, rather than pyroptosis, of macrophages. Inhibition of caspase-8 blocked YopK-dependent apoptosis, suggesting the involvement of the extrinsic pathway, and appeared cell-type specific. However, in contrast to yopJ, deletion of yopK caused a large decrease in virulence in a mouse pneumonic plague model. YopK-dependent modulation of macrophage apoptosis was observed at 6 and 24 hours post-infection (HPI). When YopK was absent, decreased populations of macrophages and dendritic cells were seen in the lungs at 24 HPI and correlated with resolution rather than progression of inflammation. Together the data suggest that Y. pestis YopK may coordinate the inflammatory response during pneumonic plague through the regulation of apoptosis of immune cells.

【 授权许可】

CC BY