Murine rotavirus infects and replicates in intestinal tuft cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE168773 | GEO | 2021/10/04
REPOSITORIES: GEO
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Project description:Murine rotavirus infects and replicates in intestinal tuft cells
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Project description:To understand the impact of murine rotavirus infection on mouse intestinal epithelial tissue, we isolated total intestinal epithelium from uninfected and infected C57Bl6J mice and performed single-cell RNAseq.
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Project description:We previously identified Dclk1, a tuft cell marker, marks tumor stem cells (TSCs) in mouse intestinal tumors. In this study, we have identified IL17RB as a cell surface marker distinctively expressed by Dclk1+ tuft-like tumor cells in mouse intestinal tumors. Using this tuft cell marker, we compared and analyzed the transcriptome of Lgr5-tuft marker-, Lgr5+tuft marker-, Lgr5-tuft marker+, and Lgr5+tuft marker+ tumor cells. These analyses revealed that tuft-like tumor cells in the intestinal tumors comprise two distinct subsets: highly differentiated tuft-like tumor cells (Lgr5-tuft marker+ cells) and tuft-like tumor cells with TCS potential (Lgr5+tuft marker+ cells).
2021-02-19 | GSE118853 | GEO
Project description:The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To clarify how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (Just EGFP Death Inducing) CD8+ T cells into tuft cell reporter mice (Gfi1b-GFP). Surprisingly, some tuft cells partially resist JEDI CD8+ T cell-mediated killing – unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells – despite seemingly normal antigen presentation. When targeting tuft cells, JEDI CD8+ T cells predominantly adopt a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. Importantly, JEDI CD8+ T cells neither clear nor prevent MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen (e.g., GFP).
2023-12-08 | GSE242118 | GEO
Project description:The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To clarify how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (Just EGFP Death Inducing) CD8+ T cells into tuft cell reporter mice (Gfi1b-GFP). Surprisingly, some tuft cells partially resist JEDI CD8+ T cell-mediated killing – unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells – despite seemingly normal antigen presentation. When targeting tuft cells, JEDI CD8+ T cells predominantly adopt a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. Importantly, JEDI CD8+ T cells neither clear nor prevent MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen (e.g., GFP).
2023-12-08 | GSE249744 | GEO
Project description:Tuft cells are an epithelial cell subset critical for initiating type 2 immune responses to parasites and protozoa in the small intestine. To respond to these stimuli, intestinal tuft cells use taste chemosensory signaling pathways, but the role of taste receptors in type 2 immunity is poorly understood. Here, we show that the taste receptor TAS1R3, which detects sweet and umami in the tongue, also regulates tuft cell responses in the distal small intestine. BALB/c mice, which have an inactive form of TAS1R3, as well as Tas1r3-deficient C57BL6/J mice both have severely impaired responses to tuft cell-inducing signals in the ileum including the protozoa Tritrichomonas muris and succinate. In contrast, TAS1R3 is not required to mount an immune response to the helminth Heligmosomoides polygyrus, which infects the proximal small intestine. Examination of uninfected Tas1r3-/- mice revealed a modest reduction in the number of tuft cells in the proximal small intestine but a severe decrease in the distal small intestine at homeostasis. Together, these results suggest that TAS1R3 influences intestinal immunity by shaping the epithelial cell landscape at steady state.
2020-01-09 | GSE140395 | GEO
Project description:Intestinal homeostasis is dynamically coordinated by various types of epithelial cells fulfilling their specific functions. Tuft cells as chemosensory cells have emerged as key players of the host response, such as innate immunity. Tuft cells are also critical for the restoration of intestinal architecture upon damage, thereby contributing to inflammatory bowel diseases (IBDs) characterized by defective intestinal barrier integrity. However, the molecular mechanism of how tuft cell homeostasis is controlled remains obscure. Recent studies have identified single-nucleotide polymorphisms in the inositol polyphosphate multikinase (IPMK) gene associated with IBD predisposition. IPMK, an essential enzyme for inositol phosphate metabolism, has been known to mediate major biological events such as growth. To investigate the functional significance of IPMK in gut epithelium, we generated intestinal epithelial cell (IEC)-specific Ipmk knockout (IPMKΔIEC) mice. Whereas IPMKΔIEC mice developed normally and showed no intestinal abnormalities during homeostasis, Ipmk deletion aggravated dextran sulfate sodium (DSS)-induced colitis, with higher clinical colitis scores, and elevated epithelial barrier permeability. Surprisingly, no apparent defects in epithelial growth signaling pathway and inflammation were found in DSS-challenged, IPMK-deficient colons. Rather, Ipmk deletion led to a significant decrease in the number of tuft cells without influencing other intestinal epithelial cells. Ipmk deletion in the gut epithelium was found to reduce choline acetyltransferase but not cytokines (e.g., IL-25), suggesting selective loss of cholinergic signaling. Single-cell RNA-sequencing of mouse colonic tuft cells (EpCAM+/Siglec F+) and immunohistochemistry revealed three populations of tuft cells and further showed that, in IPMKΔIEC mice, a transcriptionally inactive tuft club cell population was markedly expanded, and neuronal-related tuft cells were relatively decreased, supporting the abnormal development of tuft cells without IPMK functions. Thus, IPMK acts as a physiological determinant of colonic tuft cell homeostasis, thereby mediating tissue regeneration upon injury.
2022-10-26 | GSE200284 | GEO
Project description:Intestinal tuft cells are critical in anti-helminth immunity by producing IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) in order to ultimately expand both goblet and tuft cells. Translational reprogramming is involved in intestinal tuft cell differentiation but the role of tRNA modifications in this process is unknown. We show here that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of N. brasiliensis infection in mice. Elp3 is essential for the IL-13-dependent induction of some glycolytic enzymes such as Hexokinase 1 and Aldolase A and consequently links specific metabolic pathways to tuft cell differentiation. Importantly, loss of epithelial Elp3 in the intestine blocks the translation of Nprl2, a mTORC1 inhibitor, which consequently enhances mTORC1 activation and stabilizes Atf4 in both transit amplifying and progenitor cells. Likewise, Atf4 overexpression in mouse intestinal epithelium blocks tuft cell differentiation and impairs the control of intestinal helminth infection. Collectively, our data define Atf4 as a negative regulator of tuft cell differentiation and provide insights into mechanisms through which some tRNA modifications promote a type 2 immune response to parasites in the intestine.
2024-07-25 | GSE241625 | GEO
Project description:Lgr5+tuft marker+ intestinal tumor cells
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Project description:Tuft cells as a type of intestinal epithelial cells exist in epithelial barriers that play a critical role in immunity against parasite infection. It remains elusive about whether Tuft cells participate in bacterial eradication. Here we identify Sh2d6 as a signature marker for CD45+ Tuft-2 cells. Tuft-2 cells are derived from Lgr5+ intestinal stem cells but not bone marrow cells. Depletion of Tuft-2 cells is susceptible to bacterial infection. Tuft-2 cells quickly expand over bacterial infection and sense bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engagement with N-undecanoylglycine activates GPCR-PLCγ2-Ca2+ signal axis, which initiates prostaglandin D2 (PGD2) production. PGD2 enhances mucus secretion of Goblet cells and induces antibacterial immunity. Moreover, Vmn2r26 signaling also promotes SpiB expression, which is responsible for Tuft-2 cell development and expansion over bacterial challenge. Our findings reveal a novel function of Tuft-2 cells in immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites. We used microarrays to detail the gene expression of Tuft-2 cells compared with non Tuft-2 epithelial cells under Shigella infection.
2021-09-24 | GSE184675 | GEO