The β-d- manno -heptoses are immune agonists across kingdoms

Bacterial small molecule metabolites such as adenosine-diphosphate-d- -β-d- -heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea,...

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Published in:Science (American Association for the Advancement of Science) 2024-08, Vol.385 (6709), p.678-684
Main Authors: Tang, Yue, Tian, Xiaoying, Wang, Min, Cui, Yinglu, She, Yang, Shi, Zhaoxiang, Liu, Jiaqi, Mao, Huijin, Liu, Lilu, Li, Chao, Zhang, Yuwei, Li, Pengwei, Ma, Yue, Sun, Jinyuan, Du, Qing, Li, Jie, Wang, Jun, Li, De-Feng, Wu, Bian, Shao, Feng, Chen, Yihua
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Animals
Archaea - immunology
Bacteria
Eukaryotes
Flagellin
Heptoses
Humans
Immune response
Immune system
Immunity, Innate
Innate immunity
Kinases
Lipopolysaccharides
Mice
Nucleotides
Nucleotidyltransferases - metabolism
Pathogens
Prokaryotes
Vertebrates
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cites cdi_FETCH-LOGICAL-c209t-477bbf543192d6be9524876a41089d4e6b4cc3923b113a2c31f249769c3fcfa43
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container_issue 6709
container_start_page 678
container_title Science (American Association for the Advancement of Science)
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creator Tang, Yue
Tian, Xiaoying
Wang, Min
Cui, Yinglu
She, Yang
Shi, Zhaoxiang
Liu, Jiaqi
Mao, Huijin
Liu, Lilu
Li, Chao
Zhang, Yuwei
Li, Pengwei
Ma, Yue
Sun, Jinyuan
Du, Qing
Li, Jie
Wang, Jun
Li, De-Feng
Wu, Bian
Shao, Feng
Chen, Yihua
description Bacterial small molecule metabolites such as adenosine-diphosphate-d- -β-d- -heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STT motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)- and uridine-diphosphate (UDP)-heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)-dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the β-d- -heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.
doi_str_mv 10.1126/science.adk7314
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subjects Amino Acid Motifs
Animals
Archaea - immunology
Bacteria
Eukaryotes
Flagellin
Heptoses
Humans
Immune response
Immune system
Immunity, Innate
Innate immunity
Kinases
Lipopolysaccharides
Mice
Nucleotides
Nucleotidyltransferases - metabolism
Pathogens
Prokaryotes
Vertebrates
title The β-d- manno -heptoses are immune agonists across kingdoms
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