RRC ID 46307
Author De Arras L, Seng A, Lackford B, Keikhaee MR, Bowerman B, Freedman JH, Schwartz DA, Alper S.
Title An evolutionarily conserved innate immunity protein interaction network.
Journal J Biol Chem
Abstract The innate immune response plays a critical role in fighting infection; however, innate immunity also can affect the pathogenesis of a variety of diseases, including sepsis, asthma, cancer, and atherosclerosis. To identify novel regulators of innate immunity, we performed comparative genomics RNA interference screens in the nematode Caenorhabditis elegans and mouse macrophages. These screens have uncovered many candidate regulators of the response to lipopolysaccharide (LPS), several of which interact physically in multiple species to form an innate immunity protein interaction network. This protein interaction network contains several proteins in the canonical LPS-responsive TLR4 pathway as well as many novel interacting proteins. Using RNAi and overexpression studies, we show that almost every gene in this network can modulate the innate immune response in mouse cell lines. We validate the importance of this network in innate immunity regulation in vivo using available mutants in C. elegans and mice.
Volume 288(3)
Pages 1967-78
Published 2013-1-18
DOI 10.1074/jbc.M112.407205
PII M112.407205
PMID 23209288
PMC PMC3548504
MeSH Animals Biological Evolution Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / immunology* Caenorhabditis elegans Proteins / metabolism Cell Line Gene Expression / drug effects Gene Expression / immunology Humans Immunity, Innate* / drug effects Lipopolysaccharides / pharmacology Macrophages / cytology Macrophages / drug effects Macrophages / metabolism* Mice Mutation Oligonucleotide Array Sequence Analysis Protein Interaction Maps / genetics Protein Interaction Maps / immunology* RNA Interference* RNA, Small Interfering / genetics Signal Transduction / drug effects Signal Transduction / immunology Toll-Like Receptor 4 / genetics Toll-Like Receptor 4 / immunology
IF 4.106
Times Cited 17
C.elegans tm5176 tm1968