| First Author | Strine MS | Year | 2024 |
| Journal | Sci Immunol | Volume | 9 |
| Issue | 93 | Pages | eadi7038 |
| PubMed ID | 38517952 | Mgi Jnum | J:361414 |
| Mgi Id | MGI:7782804 | Doi | 10.1126/sciimmunol.adi7038 |
| Citation | Strine MS, et al. (2024) Intestinal tuft cell immune privilege enables norovirus persistence. Sci Immunol 9(93):eadi7038 |
| abstractText | The persistent murine norovirus strain MNV(CR6) is a model for human norovirus and enteric viral persistence. MNV(CR6) causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNV(CR6) induces functional MNV-specific CD8(+) T cells, these lymphocytes fail to clear infection. To examine 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 Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8(+) T cell-mediated killing-unlike Lgr5(+) intestinal stem cells and extraintestinal tuft cells-despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8(+) T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8(+) T cells neither cleared nor prevented MNV(CR6) infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8(+) T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes. |
