Activation of the innate immunity in Drosophila by endogenous chromosomal DNA that escaped apoptotic degradation.
Apoptotic cell death is accompanied by degradation of chromosomal DNA. Here, we established in Drosophila a null mutation in the gene for inhibitor of caspase-activated DNase (ICAD) by P-element insertion. We also identified a loss-of-function mutant in Drosophila for DNase II-like acid DNase. The flies deficient in the ICAD gene did not express CAD, and did not undergo apoptotic DNA fragmentation during embryogenesis and oogenesis. In contrast, the deficiency of DNase II enhanced the apoptotic DNA fragmentation in the embryos and ovary, but paradoxically, the mutant flies accumulated a large amount of DNA, particularly in the ovary. This accumulation of DNA in the DNase II mutants caused the constitutive expression of the antibacterial genes for diptericin and attacin, which are usually activated during bacterial infection. The expression of these genes was further enhanced in flies lacking both dICAD and DNase II. These results indicated that CAD and DNase II work independently to degrade chromosomal DNA during apoptosis, and if the DNA is left undigested, it can activate the innate immunity in Drosophila.
Mukae
Naomi
N
Department of Genetics, Osaka University Medical School, Osaka 565-0871, Japan.
Yokoyama
Hideki
H
Yokokura
Takakazu
T
Sakoyama
Yasuhiko
Y
Nagata
Shigekazu
S
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002875:Chromosomes / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology*; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012772:Shock, Septic / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; C488990:AttA protein, Drosophila; C488991:AttB protein, Drosophila; C488989:AttC protein, Drosophila; D017931:DNA Primers; C054756:DptA protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D011506:Proteins; D011994:Recombinant Proteins; C039711:attacin antibacterial protein, insect; C109664:caspase-activated DNase inhibitor; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II