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