Caspase-1 activation in macrophages infected with Yersinia pestis KIM requires the type III secretion system effector YopJ.
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-1beta (IL-1beta) 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-1beta 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-1beta 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-1beta 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.
Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, State University of New York at Stony Brook, New York 11794-5222, USA.
Sarit
S
Lilo
Ying
Y
Zheng
James B
JB
Bliska
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D020170:Caspase 1 / Q000172:deficiency / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015008:Yersinia enterocolitica / Q000472:pathogenicity; D015010:Yersinia pestis / Q000235:genetics / Q000472:pathogenicity*; D015011:Yersinia pseudotuberculosis / Q000472:pathogenicity
D001426:Bacterial Proteins; D053583:Interleukin-1beta; C109227:YopP protein, Yersinia; D020170:Caspase 1