Nucleolar fibrillarin is an evolutionarily conserved regulator of bacterial pathogen resistance

• Published in: Nature communications 2018-09, Vol.9 (1), p.3607-10, Article 3607
• Main Authors: Tiku, Varnesh, Kew, Chun, Mehrotra, Parul, Ganesan, Raja, Robinson, Nirmal, Antebi, Adam
• Format: Article
• Language: English
• Subjects: 13; 13/109; 13/21; 13/51; 13/89; 38/1; 38/77; 38/89; 38/90; 631/208; 631/250/254; 631/250/262/2106; 631/80; Animals; Animals, Genetically Modified; Bacteria; Bacterial infections; Caenorhabditis elegans - genetics; Caenorhabditis elegans - microbiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Nucleolus - metabolism; Cell Nucleolus - microbiology; Cell Nucleolus - pathology; Cell survival; Chromosomal Proteins, Non-Histone - metabolism; Disease Resistance; Enterococcus faecalis - pathogenicity; Epistasis; Evolution, Molecular; Female; Fibrillarin; Gene Knockdown Techniques; HeLa Cells - microbiology; Host-Pathogen Interactions; Humanities and Social Sciences; Humans; Immune clearance; Immune response; Immunity; Immunity (Disease); Infections; Innate immunity; Mammalian cells; Mice, Inbred C57BL; multidisciplinary; Mutation; Nucleoli; Pathogens; Proteins; Pseudomonas aeruginosa - pathogenicity; Resistance factors; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Staphylococcus aureus - pathogenicity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06051-1

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. Innate immunity is critical in the response to bacterial infection. Here the authors show a role for the nucleolar-associated protein fibrillarin in regulating the innate response to infection.