期刊
CELL
卷 183, 期 2, 页码 411-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.08.048
关键词
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资金
- Ecole Doctorale Frontieres de l'Innovation en Recherche et Education - Programme Bettencourt
- ITMO Cancer-Aviesan
- Fondation pour la Recherche Medicale
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [772487]
- DCBIOL Labex [ANR-10-IDEX-0001-02-PSL, ANR-11-LABX-0043]
- Institut National Du Cancer
- US National Institute of Health [R01 DK113136, DK121977]
- Agence Nationale de la Recherche (Investissements d'Avenir'' program) [ANR-10-EQPX-03, ANR-10-INBS-09-08]
- Canceropole lle-de-France
- SiRIC-Curie program (SiRIC grant) [INCa-DGOS-4654]
- European Research Council (ERC) [772487] Funding Source: European Research Council (ERC)
The colon is primarily responsible for absorbing fluids. It contains a large number of microorganisms including fungi, which are enriched in its distal segment. The colonic mucosa must therefore tightly regulate fluid influx to control absorption of fungal metabolites, which can be toxic to epithelial cells and lead to barrier dysfunction. How this is achieved remains unknown. Here, we describe a mechanism by which the innate immune system allows rapid quality check of absorbed fluids to avoid intoxication of colonocytes. This mechanism relies on a population of distal colon macrophages that are equipped with balloon-like protrusions (BLPs) inserted in the epithelium, which sample absorbed fluids. In the absence of macrophages or BLPs, epithelial cells keep absorbing fluids containing fungal products, leading to their death and subsequent loss of epithelial barrier integrity. These results reveal an unexpected and essential role of macrophages in the maintenance of colon-microbiota interactions in homeostasis.
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