| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Snyder, Annelise G. Philip, Naomi H. Wei, Lei Oberst, Andrew Shin, Sunny Green, Douglas R. Dillon, Christopher P. Parker, Matthew Zhang, Jinghui Mauldin, Elizabeth A. Fitzgerald, Louise Wynosky-dolfi, Meghan A. Copenhaver, Alan M. Zwack, Erin E. Fitzgerald, Patrick Hu, Baofeng Brodsky, Igor E. |
| Description |
Author Affiliation: Philip NH ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); Dillon CP ( Departments of Immunology and.); Snyder AG ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); Fitzgerald P ( Departments of Immunology and.); Wynosky-Dolfi MA ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); Zwack EE ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); Hu B ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); Fitzgerald L ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); Mauldin EA ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); Copenhaver AM ( Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104); Shin S ( Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104); Wei L ( Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY 14263); Parker M ( Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105); Zhang J ( Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105); Oberst A ( Department of Immunology, University of Washington, Seattle, WA 98109.); Green DR ( Departments of Immunology and.); Brodsky IE ( Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104); |
| Abstract |
Toll-like receptor signaling and subsequent activation of NF-κB- and MAPK-dependent genes during infection play an important role in antimicrobial host defense. The YopJ protein of pathogenic Yersinia species inhibits NF-κB and MAPK signaling, resulting in blockade of NF-κB-dependent cytokine production and target cell death. Nevertheless, Yersinia infection induces inflammatory responses in vivo. Moreover, increasing the extent of YopJ-dependent cytotoxicity induced by Yersinia pestis and Yersinia pseudotuberculosis paradoxically leads to decreased virulence in vivo, suggesting that cell death promotes anti-Yersinia host defense. However, the specific pathways responsible for YopJ-induced cell death and how this cell death mediates immune defense against Yersinia remain poorly defined. YopJ activity induces processing of multiple caspases, including caspase-1, independently of inflammasome components or the adaptor protein ASC. Unexpectedly, caspase-1 activation in response to the activity of YopJ required caspase-8, receptor-interacting serine/threonine kinase 1 (RIPK1), and Fas-associated death domain (FADD), but not RIPK3. Furthermore, whereas RIPK3 deficiency did not affect YopJ-induced cell death or caspase-1 activation, deficiency of both RIPK3 and caspase-8 or FADD completely abrogated Yersinia-induced cell death and caspase-1 activation. Mice lacking RIPK3 and caspase-8 in their hematopoietic compartment showed extreme susceptibility to Yersinia and were deficient in monocyte and neutrophil-derived production of proinflammatory cytokines. Our data demonstrate for the first time to our knowledge that RIPK1, FADD, and caspase-8 are required for YopJ-induced cell death and caspase-1 activation and suggest that caspase-8-mediated cell death overrides blockade of immune signaling by YopJ to promote anti-Yersinia immune defense. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
20 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-05-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Caspase 1 Metabolism Caspase 8 Immunity, Innate MAP Kinase Signaling System NF-kappa B Animals Apoptosis Bacterial Proteins Genetics Enzyme Activation Fas-Associated Death Domain Protein Gene Expression Regulation, Enzymologic Mice Mice, Transgenic Receptor-Interacting Protein Serine-Threonine Kinases Yersinia Infections Microbiology Yersinia Pseudotuberculosis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
