The β- <scp>d</scp> - <i>manno</i> -heptoses are immune agonists across kingdoms-Reference-Cited by-同舟云学术

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

Published:2024-08-09 Issue:6709 Volume:385 Page:678-684
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Tang Yue¹^ORCID,Tian Xiaoying²³^ORCID,Wang Min¹⁴^ORCID,Cui Yinglu¹^ORCID,She Yang²^ORCID,Shi Zhaoxiang⁵,Liu Jiaqi²³^ORCID,Mao Huijin¹⁶,Liu Lilu¹⁶,Li Chao¹⁶,Zhang Yuwei¹^ORCID,Li Pengwei¹^ORCID,Ma Yue⁷^ORCID,Sun Jinyuan¹⁶,Du Qing¹⁶^ORCID,Li Jie¹⁶^ORCID,Wang Jun⁶⁷,Li De-feng¹⁶^ORCID,Wu Bian¹⁸^ORCID,Shao Feng²⁹¹⁰^ORCID,Chen Yihua¹⁶^ORCID

Affiliation:

1. State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

2. National Institute of Biological Sciences, Beijing 102206, China.

3. Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 102206, China.

4. College of New Materials and Chemical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, China.

5. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 117004, China.

6. University of Chinese Academy of Sciences, Beijing 100049, China.

7. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

8. College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China.

9. Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China.

10. New Cornerstone Science Laboratory, Shenzhen 518054, China.

Abstract

Bacterial small molecule metabolites such as adenosine-diphosphate- d - glycero -β- d - manno -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 R5 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 - manno -heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adk7314

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