RRC ID 59414
Author Tiku V, Kew C, Mehrotra P, Ganesan R, Robinson N, Antebi A.
Title Nucleolar fibrillarin is an evolutionarily conserved regulator of bacterial pathogen resistance.
Journal Nat Commun
Abstract Innate immunity is the first line of defense against infections. Pathways regulating innate responses can also modulate other processes, including stress resistance and longevity. Increasing evidence suggests a role for the nucleolus in regulating cellular processes implicated in health and disease. Here we show the highly conserved nucleolar protein, fibrillarin, is a vital factor regulating pathogen resistance. Fibrillarin knockdown enhances resistance in C. elegans against bacterial pathogens, higher levels of fibrillarin induce susceptibility to infection. Pathogenic infection reduces nucleolar size, ribsosomal RNA, and fibrillarin levels. Genetic epistasis reveals fibrillarin functions independently of the major innate immunity mediators, suggesting novel mechanisms of pathogen resistance. Bacterial infection also reduces nucleolar size and fibrillarin levels in mammalian cells. Fibrillarin knockdown prior to infection increases intracellular bacterial clearance, reduces inflammation, and enhances cell survival. Collectively, these findings reveal an evolutionarily conserved role of fibrillarin in infection resistance and suggest the nucleolus as a focal point in innate immune responses.
Volume 9(1)
Pages 3607
Published 2018-9-6
DOI 10.1038/s41467-018-06051-1
PII 10.1038/s41467-018-06051-1
PMID 30190478
PMC PMC6127302
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / microbiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleolus / metabolism Cell Nucleolus / microbiology Cell Nucleolus / pathology Chromosomal Proteins, Non-Histone / metabolism Disease Resistance* Enterococcus faecalis / pathogenicity Evolution, Molecular Female Gene Knockdown Techniques HeLa Cells / microbiology Host-Pathogen Interactions* Humans Mice, Inbred C57BL Mutation Pseudomonas aeruginosa / pathogenicity Staphylococcus aureus / pathogenicity
IF 11.878
Times Cited 6
C.elegans tm1978