Experiment Id | GSE249744 | Name | Immune-privileged intestinal tuft cells enable norovirus persistence II |
Experiment Type | RNA-Seq | Study Type | Baseline |
Source | GEO | Curation Date | 2025-02-03 |
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). To investigate the effector function of JEDI CD8+ T cells in the colonic epithelium of mice targeting Gfi1b-GFP+ tuft cells or Lgr5-GFP+ stem cells |