@article{05ee88943ffc4c898557260c32048c0c,
title = "A complex immune response to flagellin epitope variation in commensal communities",
abstract = "Immune systems restrict microbial pathogens by identifying “non-self” molecules called microbe-associated molecular patterns (MAMPs). It is unclear how immune responses are tuned to or by MAMP diversity present in commensal microbiota. We systematically studied the variability of commensal peptide derivatives of flagellin (flg22), a MAMP detected by plants. We define substantial functional diversity. Most flg22 peptides evade recognition, while others contribute to evasion by manipulating immunity through antagonism and signal modulation. We establish a paradigm of signal integration, wherein the sequential signaling outputs of the flagellin receptor are separable and allow for reprogramming by commensal-derived flg22 epitope variants. Plant-associated communities are enriched for immune evading flg22 epitopes, but upon physiological stress that represses the immune system, immune-activating flg22 epitopes become enriched. The existence of immune-manipulating epitopes suggests that they evolved to either communicate or utilize the immune system for host colonization and thus can influence commensal microbiota community composition.",
keywords = "Ralstonia, bacterial evolution, community formation, flagellin, host-microbe interactions, ligand-receptor interactions, pattern recognition receptors, plant immunity, plant microbiome, receptor antagonism",
author = "Colaianni, {Nicholas R.} and Katarzyna Parys and Lee, {Ho Seok} and Conway, {Jonathan M.} and Kim, {Nak Hyun} and Natalie Edelbacher and Mucyn, {Tatiana S.} and Mathias Madalinski and Law, {Theresa F.} and Jones, {Corbin D.} and Youssef Belkhadir and Dangl, {Jeffery L.}",
note = "Funding Information: This work was supported by NSF grant IOS-1917270 to C.D.J. and J.L.D.; J.L.D. is an investigator of the Howard Hughes Medical Institute, supported by the HHMI . N.R.C. was supported by the NIH training grant T32GM135123 . The work was also supported by grants from the Austrian Academy of Sciences through the Gregor Mendel Institute, the Vienna Science and Technology Fund project ( LS17-047 ) and by the FWF Austrian Science Fund ( I 3654 ) to Y.B. We thank the GMI/IMBA/IMP Protein Chemistry Core facility for mass spectrometry analysis and the Vienna Biocenter Core Facilities (VBCF ProTech) for help with protein production. We thank members of the Dangl and Belkhadir labs for useful discussion, and Drs. Sarah Grant, Oliver Furzer, and Sarah Gilbert for critical reading of the manuscript. We thank JiWoo Kim for her help with confocal imaging. We also thank Dr. Niko Geldner for kindly providing us proUBQ10:FLS2-GFP seeds. Funding Information: This work was supported by NSF grant IOS-1917270 to C.D.J. and J.L.D.; J.L.D. is an investigator of the Howard Hughes Medical Institute, supported by the HHMI. N.R.C. was supported by the NIH training grant T32GM135123. The work was also supported by grants from the Austrian Academy of Sciences through the Gregor Mendel Institute, the Vienna Science and Technology Fund project (LS17-047) and by the FWF Austrian Science Fund (I 3654) to Y.B. We thank the GMI/IMBA/IMP Protein Chemistry Core facility for mass spectrometry analysis and the Vienna Biocenter Core Facilities (VBCF ProTech) for help with protein production. We thank members of the Dangl and Belkhadir labs for useful discussion, and Drs. Sarah Grant, Oliver Furzer, and Sarah Gilbert for critical reading of the manuscript. We thank JiWoo Kim for her help with confocal imaging. We also thank Dr. Niko Geldner for kindly providing us proUBQ10:FLS2-GFP seeds. N.R.C. C.D.J. Y.B. and J.L.D. conceptualized the project. C.D.J. Y.B. and J.L.D. supervised the research. N.R.C. K.P. H.-S.L. J.M.C. N.H.K. N.E. T.S.M. and T.F.L. performed experiments. M.M. synthesized peptides and performed quality control. All authors contributed to data analysis. N.R.C. developed figures and wrote the main draft of the text. C.D.J. Y.B. and J.L.D. contributed significantly to that draft and all other authors contributed edits and comments to finalize the paper. J.L.D. is a co-founder of, and shareholder in, AgBiome LLC, a corporation whose goal is to use plant-associated microbes to improve plant productivity. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = apr,
day = "14",
doi = "10.1016/j.chom.2021.02.006",
language = "English (US)",
volume = "29",
pages = "635--649.e9",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "4",
}