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Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon

Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many di...

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Autores principales: Lei, Hao, Yu, Defu, Xue, Yan-Bo, Li, Yi-Hong, Gong, Shi-Meng, Peng, Yuan-Yuan, Liu, Kai-Fang, Buratto, Damiano, Yang, Yisen, Zhang, Sai-Sai, Wu, Min, Zhou, Ruhong, Huang, Liquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634341/
https://www.ncbi.nlm.nih.gov/pubmed/37954611
http://dx.doi.org/10.3389/fimmu.2023.1259521
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author Lei, Hao
Yu, Defu
Xue, Yan-Bo
Li, Yi-Hong
Gong, Shi-Meng
Peng, Yuan-Yuan
Liu, Kai-Fang
Buratto, Damiano
Yang, Yisen
Zhang, Sai-Sai
Wu, Min
Zhou, Ruhong
Huang, Liquan
author_facet Lei, Hao
Yu, Defu
Xue, Yan-Bo
Li, Yi-Hong
Gong, Shi-Meng
Peng, Yuan-Yuan
Liu, Kai-Fang
Buratto, Damiano
Yang, Yisen
Zhang, Sai-Sai
Wu, Min
Zhou, Ruhong
Huang, Liquan
author_sort Lei, Hao
collection PubMed
description Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many different types of pathogens they can sense or what exact molecular mechanisms they employ to initiate targeted responses. In this study, we found that an anaerobic pathobiont microbe, Ruminococcus gnavus (R. gnavus), can induce tuft cell proliferation in the proximal colon whereas the microbe’s lysate can stimulate these proximal colonic tuft cells to release interleukin-25 (IL-25). Nullification of the Gng13 and Trpm5 genes that encode the G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, or application of the Tas2r inhibitor allyl isothiocyanate (AITC), G protein Gβγ subunit inhibitor Gallein or the phospholipase Cβ2 (PLCβ2) inhibitor U73122 reduces R. gnavus-elicited tuft cell proliferation or IL-25 release or both. Furthermore, Gng13 conditional knockout or Trpm5 knockout diminishes the expression of gasdermins C2, C3 and C4, and concomitantly increases the activated forms of caspases 3, 8 and 9 as well as the number of TUNEL-positive apoptotic cells in the proximal colon. Together, our data suggest that taste signal transduction pathways are not only involved in the detection of R. gnavus infection, but also contribute to helping maintain gasdermin expression and prevent apoptotic cell death in the proximal colon, and these findings provide another strategy to combat R. gnavus infection and sheds light on new roles of taste signaling proteins along with gasdermins in protecting the integrity of the proximal colonic epithelium.
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spelling pubmed-106343412023-11-10 Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon Lei, Hao Yu, Defu Xue, Yan-Bo Li, Yi-Hong Gong, Shi-Meng Peng, Yuan-Yuan Liu, Kai-Fang Buratto, Damiano Yang, Yisen Zhang, Sai-Sai Wu, Min Zhou, Ruhong Huang, Liquan Front Immunol Immunology Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many different types of pathogens they can sense or what exact molecular mechanisms they employ to initiate targeted responses. In this study, we found that an anaerobic pathobiont microbe, Ruminococcus gnavus (R. gnavus), can induce tuft cell proliferation in the proximal colon whereas the microbe’s lysate can stimulate these proximal colonic tuft cells to release interleukin-25 (IL-25). Nullification of the Gng13 and Trpm5 genes that encode the G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, or application of the Tas2r inhibitor allyl isothiocyanate (AITC), G protein Gβγ subunit inhibitor Gallein or the phospholipase Cβ2 (PLCβ2) inhibitor U73122 reduces R. gnavus-elicited tuft cell proliferation or IL-25 release or both. Furthermore, Gng13 conditional knockout or Trpm5 knockout diminishes the expression of gasdermins C2, C3 and C4, and concomitantly increases the activated forms of caspases 3, 8 and 9 as well as the number of TUNEL-positive apoptotic cells in the proximal colon. Together, our data suggest that taste signal transduction pathways are not only involved in the detection of R. gnavus infection, but also contribute to helping maintain gasdermin expression and prevent apoptotic cell death in the proximal colon, and these findings provide another strategy to combat R. gnavus infection and sheds light on new roles of taste signaling proteins along with gasdermins in protecting the integrity of the proximal colonic epithelium. Frontiers Media S.A. 2023-10-25 /pmc/articles/PMC10634341/ /pubmed/37954611 http://dx.doi.org/10.3389/fimmu.2023.1259521 Text en Copyright © 2023 Lei, Yu, Xue, Li, Gong, Peng, Liu, Buratto, Yang, Zhang, Wu, Zhou and Huang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lei, Hao
Yu, Defu
Xue, Yan-Bo
Li, Yi-Hong
Gong, Shi-Meng
Peng, Yuan-Yuan
Liu, Kai-Fang
Buratto, Damiano
Yang, Yisen
Zhang, Sai-Sai
Wu, Min
Zhou, Ruhong
Huang, Liquan
Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon
title Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon
title_full Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon
title_fullStr Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon
title_full_unstemmed Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon
title_short Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon
title_sort tuft cells utilize taste signaling molecules to respond to the pathobiont microbe ruminococcus gnavus in the proximal colon
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634341/
https://www.ncbi.nlm.nih.gov/pubmed/37954611
http://dx.doi.org/10.3389/fimmu.2023.1259521
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