Caspase-1 activation in macrophages infected with Yersinia pestis KIM requires the type III secretion system effector YopJ

被引:56
作者
Lilo, Sarit
Zheng, Ying
Bliska, James B. [1 ]
机构
[1] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
关键词
D O I
10.1128/IAI.01695-07
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pathogenic Yersinia species utilize a type III secretion system (T3SS) to translocate effectors called Yersinia outer proteins (Yops) into infected host cells. Previous studies demonstrated a role for effector Yops in the inhibition of caspase-1-mediated cell death and secretion of interleukin-1 beta (IL-1 beta) in naive macrophages infected with Yersinia enterocolitica. Naive murine macrophages were infected with a panel of different Yersinia pestis and Yersinia pseudotuberculosis strains to determine whether Yops of these species inhibit caspase-1 activation. Cell death was measured by release of lactate dehydrogenase (LDH), and enzyme-linked immunosorbent assay for secreted IL-1 beta was used to measure caspase-1 activation. Surprisingly, isolates derived from the Y. pestis KIM strain (e. g., KIM5) displayed an unusual ability to activate caspase-1 and kill infected macrophages compared to other Y. pestis and Y. pseudotuberculosis strains tested. Secretion of IL-1 beta following KIM5 infection was reduced in caspase-1-deficient macrophages compared to wild-type macrophages. However, release of LDH was not reduced in caspase-1-deficient macrophages, indicating that cell death occurred independently of caspase-1. Analysis of KIM-derived strains defective for production of functional effector or translocator Yops indicated that translocation of catalytically active YopJ into macrophages was required for caspase-1 activation and cell death. Release of LDH and secretion of IL-1 beta were not reduced when actin polymerization was inhibited in KIM5-infected macrophages, indicating that extracellular bacteria translocating YopJ could trigger cell death and caspase-1 activation. This study uncovered a novel role for YopJ in the activation of caspase-1 in macrophages.
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收藏
页码:3911 / 3923
页数:13
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