2. Academic Validation
  3. Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine

Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine

  • Immunity. 2022 Apr 12;55(4):686-700.e7. doi: 10.1016/j.immuni.2022.03.001.
Zhen Xiong 1,  Xiaoxiao Zhu 2,  Jingjing Geng 3,  Yuwei Xu 4,  Runyuan Wu 5,  Cunzhen Li 5,  Dongdong Fan 2,  Xiwen Qin 5,  Ying Du 6,  Yong Tian 7,  Zusen Fan 8
Affiliations

Affiliations

  • 1 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of RNA Biology of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 2 Key Laboratory of RNA Biology of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 3 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of RNA Biology of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 5 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 6 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 7 Key Laboratory of RNA Biology of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: ytian@ibp.ac.cn.
  • 8 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: fanz@moon.ibp.ac.cn.
PMID: 35320705 DOI: 10.1016/j.immuni.2022.03.001
Abstract

Tuft cells are a type of intestinal epithelial cells that exist in epithelial barriers and play a critical role in immunity against parasite Infection. It remains insufficiently clear whether Tuft cells participate in Bacterial eradication. Here, we identified Sh2d6 as a signature marker for CD45+ Tuft-2 cells. Depletion of Tuft-2 cells resulted in susceptibility to Bacterial infection. Tuft-2 cells quickly expanded in response to Bacterial infection and sensed the Bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engaged with N-undecanoylglycine activated G-protein-coupled receptor-phospholipase C gamma2 (GPCR-PLCγ2)-Ca2+ signaling axis, which initiated prostaglandin D2 (PGD2) production. PGD2 enhanced the mucus secretion of goblet cells and induced Antibacterial immunity. Moreover, Vmn2r26 signaling also promoted SpiB transcription factor expression, which is responsible for Tuft-2 cell development and expansion in response to Bacterial challenge. Our findings reveal an additional function of Tuft-2 cells in immunity against Bacterial infection through Vmn2r26-mediated recognition of Bacterial metabolites.

Keywords

N-undecanoylglycine; PGD2; SpiB; Tuft-2 cell; Vmn2r26.

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