Williams, Ashley B., Heider, Felix, Messling, Jan-Erik ORCID: 0000-0003-3843-0041, Rieckher, Matthias ORCID: 0000-0002-1945-9474, Bloch, Wilhelm and Schumacher, Bjoern (2019). Restoration of Proteostasis in the Endoplasmic Reticulum Reverses an Inflammation-Like Response to Cytoplasmic DNA in Caenorhabditis elegans. Genetics, 212 (4). S. 1259 - 1279. BETHESDA: GENETICS SOCIETY AMERICA. ISSN 1943-2631

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Abstract

Innate immune responses protect organisms against various insults, but may lead to tissue damage when aberrantly activated. In higher organisms, cytoplasmic DNA can trigger inflammatory responses that can lead to tissue degeneration. Simpler metazoan models could shed new mechanistic light on how inflammatory responses to cytoplasmic DNA lead to pathologies. Here, we show that in a DNase II-defective Caenorhabditis elegans strain, persistent cytoplasmic DNA leads to systemic tissue degeneration and loss of tissue functionality due to impaired proteostasis. These pathological outcomes can be therapeutically alleviated by restoring protein homeostasis, either via ectopic induction of the ER unfolded protein response or N-acetylglucosamine treatment. Our results establish C. elegans as an ancestral metazoan model for studying the outcomes of inflammation-like conditions caused by persistent cytoplasmic DNA and provide insight into potential therapies for human conditions involving chronic inflammation. Caenorhabditis elegans possesses a rudimentary innate immune response that serves as a model for various aspects of the human innate immune response. To date, a nematode response to pathogenic cytoplasmic DNA has not been identified...

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Williams, Ashley B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heider, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Messling, Jan-ErikUNSPECIFIEDorcid.org/0000-0003-3843-0041UNSPECIFIED
Rieckher, MatthiasUNSPECIFIEDorcid.org/0000-0002-1945-9474UNSPECIFIED
Bloch, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-145414
DOI: 10.1534/genetics.119.302422
Journal or Publication Title: Genetics
Volume: 212
Number: 4
Page Range: S. 1259 - 1279
Date: 2019
Publisher: GENETICS SOCIETY AMERICA
Place of Publication: BETHESDA
ISSN: 1943-2631
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
UNFOLDED PROTEIN RESPONSE; TOLL-LIKE RECEPTOR; C. ELEGANS; MITOCHONDRIAL-DNA; ER STRESS; LIFE-SPAN; IN-VIVO; IMMUNE; PATHWAY; ACTIVATIONMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14541

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