Journal article

Comprehensive RNAi-based screening of human and mouse TLR pathways identifies species-specific preferences in signaling protein use

Jing Sun, Ning Li, Kyu-Seon Oh, Bhaskar Dutta, Sharat J Vayttaden, Bin Lin, Thomas S Ebert, Dominic De Nardo, Joie Davis, Rustam Bagirzadeh, Nicolas W Lounsbury, Chandrashekhar Pasare, Eicke Latz, Veit Hornung, Iain DC Fraser

Science Signaling | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2016

Abstract

Toll-like receptors (TLRs) are a major class of pattern recognition receptors, which mediate the responses of innate immune cells to microbial stimuli. To systematically determine the roles of proteins in canonical TLR signaling pathways, we conducted an RNA interference (RNAi)-based screen in human and mouse macrophages. We observed a pattern of conserved signaling module dependencies across species, but found notable species-specific requirements at the level of individual proteins. Among these, we identified unexpected differences in the involvement of members of the interleukin-1 receptor-associated kinase (IRAK) family between the human and mouse TLR pathways. Whereas TLR signaling in m..

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Grants

Awarded by German Research Foundation


Awarded by European Research Council


Awarded by NIH


Awarded by Deutsche Forschungsgemeinschaft


Awarded by NIAID


Awarded by Welch Foundation


Awarded by NIH Integrative Immunology Training program grant


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) (to J. S., N. L., K.-S. O., B. D., S. J. V., B. L., J. D., N. W. L., and I. D. C. F.) and the BONFOR research commission at the University of Bonn (to D. D. N.). V. H. and T. S. E. are supported by grants from the German Research Foundation (SFB704 and SFB670) and the European Research Council (ERC-2009-StG 243046). E. L. is supported by grants from the NIH (R01HL112661), the Deutsche Forschungsgemeinschaft (SFB670), and the European Research Council (ERC InflammAct). E. L. and V. H. are members of the ImmunoSensation cluster of excellence. C. P. is supported by grants from the NIAID (AI082265) and The Welch Foundation (I-1820). R. B. is supported by an NIH Integrative Immunology Training program grant (5T32-AI005284-35).