An Evolutionarily Conserved Innate Immunity Protein Interaction Network

作者：De Arras Lesly; Seng Amara; Lackford Brad; Keikhaee Mohammad R; Bowerman Bruce; Freedman Jonathan H; Schwartz David A; Alper Scott^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288(3): 1967-1978.

DOI：10.1074/jbc.M112.407205

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.

• 出版日期2013-1-18