RRC ID |
45828
|
著者 |
Pellegrino MW, Nargund AM, Kirienko NV, Gillis R, Fiorese CJ, Haynes CM.
|
タイトル |
Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection.
|
ジャーナル |
Nature
|
Abstract |
Metazoans identify and eliminate bacterial pathogens in microbe-rich environments such as the intestinal lumen; however, the mechanisms are unclear. Host cells could potentially use intracellular surveillance or stress response programs to detect pathogens that target monitored cellular activities and then initiate innate immune responses. Mitochondrial function is evaluated by monitoring mitochondrial protein import efficiency of the transcription factor ATFS-1, which mediates the mitochondrial unfolded protein response (UPR(mt)). During mitochondrial stress, mitochondrial import is impaired, allowing ATFS-1 to traffic to the nucleus where it mediates a transcriptional response to re-establish mitochondrial homeostasis. Here we examined the role of ATFS-1 in Caenorhabditis elegans during pathogen exposure, because during mitochondrial stress ATFS-1 induced not only mitochondrial protective genes but also innate immune genes that included a secreted lysozyme and anti-microbial peptides. Exposure to the pathogen Pseudomonas aeruginosa caused mitochondrial dysfunction and activation of the UPR(mt). C. elegans lacking atfs-1 were susceptible to P. aeruginosa, whereas hyper-activation of ATFS-1 and the UPR(mt) improved clearance of P. aeruginosa from the intestine and prolonged C. elegans survival in a manner mainly independent of known innate immune pathways. We propose that ATFS-1 import efficiency and the UPR(mt) is a means to detect pathogens that target mitochondria and initiate a protective innate immune response.
|
巻・号 |
516(7531)
|
ページ |
414-7
|
公開日 |
2014-12-18
|
DOI |
10.1038/nature13818
|
PII |
nature13818
|
PMID |
25274306
|
PMC |
PMC4270954
|
MeSH |
Animals
Caenorhabditis elegans / immunology*
Caenorhabditis elegans / microbiology
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / immunology
Caenorhabditis elegans Proteins / metabolism
Host-Pathogen Interactions / immunology
Immunity, Innate / immunology*
Mitochondria / immunology*
Pseudomonas aeruginosa / physiology
Stress, Physiological / immunology
Transcription Factors / genetics
Transcription Factors / metabolism
Unfolded Protein Response / immunology*
|
IF |
42.779
|
引用数 |
121
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
線虫 |
tm4919
tm4248
tm4525 |