Universität zu Köln

Tiku, Varnesh, Kew, Chun, Mehrotra, Parul, Ganesan, Raja, Robinson, Nirmal ORCID: 0000-0002-7361-9491 and Antebi, Adam (2018). Nucleolar fibrillarin is an evolutionarily conserved regulator of bacterial pathogen resistance. Nat. Commun., 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tiku, Varnesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Kew, Chun UNSPECIFIED UNSPECIFIED UNSPECIFIED Mehrotra, Parul UNSPECIFIED UNSPECIFIED UNSPECIFIED Ganesan, Raja UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, Nirmal UNSPECIFIED orcid.org/0000-0002-7361-9491 UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-173197
DOI:	10.1038/s41467-018-06051-1
Journal or Publication Title:	Nat. Commun.
Volume:	9
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PSEUDOMONAS-AERUGINOSA EXOTOXIN; CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; HOST-DEFENSE; LIFE-SPAN; TRANSLATIONAL INHIBITION; MICROBIAL PATHOGENESIS; TRIGGERED IMMUNITY; RIBOSOMAL-RNA; GENES Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17319