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Infection and Immunity, September 2008, p. 3911-3923, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.01695-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Caspase-1 Activation in Macrophages Infected with Yersinia pestis KIM Requires the Type III Secretion System Effector YopJ{triangledown}

Sarit Lilo, Ying Zheng, and James B. Bliska*

Department of Molecular Genetics and Microbiology and Center for Infectious Diseases, State University of New York at Stony Brook, Stony Brook, New York 11794

Received 19 December 2007/ Returned for modification 24 January 2008/ Accepted 30 May 2008

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-1β (IL-1β) in naïve macrophages infected with Yersinia enterocolitica. Naïve 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-1β 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-1β 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-1β 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.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology and Center for Infectious Diseases, SUNY at Stony Brook, Stony Brook, NY 11794-5222. Phone: (631) 632-8782. Fax: (631) 632-9797. E-mail: jbliska{at}ms.cc.sunysb.edu

{triangledown} Published ahead of print on 16 June 2008.

Editor: A. J. Bäumler

Infection and Immunity, September 2008, p. 3911-3923, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.01695-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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