Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing

Programmed cell death (PCD) in mammals has been implicated in several disease states including cancer, autoimmune disease, and neurodegenerative disease. In Caenorhabditis elegans, PCD is a normal component of development. We find that Salmonella typhimurium colonization of the C. elegans intestine leads to an increased level of cell death in the worm gonad. S. typhimurium-mediated germ-line cell death is not observed in C. elegans ced-3 and ced-4 mutants in which developmentally regulated cell death is blocked, and ced-3 and ced-4 mutants are hypersensitive to S. typhimurium-mediated killing. These results suggest that PCD may be involved in the C. elegans defense response to pathogen attack.

[1]  M. Hengartner.  Apoptosis CED-4 is a stranger no more , 1997, Nature.

[2]  J. Thomas,et al.  Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[3]  C. Kurz,et al.  Caenorhabditis elegans for the study of host-pathogen interactions. , 2000, Trends in microbiology.

[4]  E. Hohmann,et al.  Pilot Study of phoP/phoQ-DeletedSalmonella enterica Serovar Typhimurium ExpressingHelicobacter pylori Urease in Adult Volunteers , 2000, Infection and Immunity.

[5]  AC Tose.  Cell , 1993, Cell.

[6]  S. Brenner.  The genetics of Caenorhabditis elegans. , 1974, Genetics.

[7]  H. Horvitz,et al.  Two C. elegans genes control the programmed deaths of specific cells in the pharynx. , 1991, Development.

[8]  Frederick M. Ausubel,et al.  Molecular Mechanisms of Bacterial Virulence Elucidated Using a Pseudomonas aeruginosa– Caenorhabditis elegans Pathogenesis Model , 1999, Cell.

[9]  W. Wood.  The Nematode Caenorhabditis elegans , 1988 .

[10]  C. Thompson,et al.  Apoptosis in the pathogenesis and treatment of disease , 1995, Science.

[11]  S. Milstein,et al.  A conserved checkpoint pathway mediates DNA damage--induced apoptosis and cell cycle arrest in C. elegans. , 2000, Molecular cell.

[12]  A. Mccarthy.  Development , 1996, Current Opinion in Neurobiology.

[13]  A. Chinnaiyan,et al.  Interaction of CED-4 with CED-3 and CED-9: A Molecular Framework for Cell Death , 1997, Science.

[14]  C. Kurz,et al.  Caenorhabditis elegans is a model host for Salmonella typhimurium , 2000, Current Biology.

[15]  H. Horvitz,et al.  The C. elegans Protein EGL-1 Is Required for Programmed Cell Death and Interacts with the Bcl-2–like Protein CED-9 , 1998, Cell.

[16]  J. Sulston,et al.  Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. , 1983, Science.

[17]  E. Groisman,et al.  The role of the PhoP/PhoQ regulon in Salmonella virulence. , 1994, Research in microbiology.

[18]  H. Horvitz,et al.  The genetics of programmed cell death in the nematode Caenorhabditis elegans. , 1994, Cold Spring Harbor symposia on quantitative biology.

[19]  M. Hengartner,et al.  Caenorhabditis elegans gene ced-9 protects cells from programmed cell death , 1992, Nature.

[20]  C. Kenyon,et al.  The nematode Caenorhabditis elegans. , 1988, Science.

[21]  F. Lang,et al.  CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. , 2000, Science.

[22]  B. Bainbridge,et al.  Genetics , 1981, Experientia.

[23]  C. Wray,et al.  Experimental Salmonella typhimurium infection in calves. , 1978, Research in veterinary science.

[24]  J. Sulston,et al.  Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. , 1977, Developmental biology.

[25]  J. Tschopp,et al.  Direct physical interaction between the Caenorhabditis elegans ‘death proteins’ CED‐3 and CED‐4 , 1997, FEBS letters.

[26]  A D Chisholm,et al.  Cell Lineage , 1898, The American Naturalist.

[27]  F. Ausubel,et al.  Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Sulston,et al.  The embryonic cell lineage of the nematode Caenorhabditis elegans. , 1983, Developmental biology.

[29]  M. Spector,et al.  Interaction between the C. elegans cell-death regulators CED-9 and CED-4 , 1997, Nature.

[30]  Xiaodong Wang,et al.  Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3 , 1997, Cell.

[31]  F. Ausubel,et al.  Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans , 2000, Current Biology.

[32]  Shai Shaham,et al.  The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme , 1993, Cell.

[33]  H. Horvitz,et al.  Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. , 1999, Development.

[34]  F. Ausubel,et al.  Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. Saraste,et al.  FEBS Lett , 2000 .