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Status |
Public on Jan 03, 2025 |
Title |
Commensal protists regulate intestinal CD8+ T cells to shape mucosal immune memory |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Tissue and microbial cues regulate the abundance and function of CD8+ T cells at barrier sites, yet the impact of specific microbes on their long-term durability remains unclear. Here, we show that the commensal protist Tritrichomonas musculus (T. mu) depletes intestinal CD8+ T cells, particularly tissue resident memory (TRM) cells, through activation of localized type 2 immunity. Colonization with T. mu or administration of its major secreted metabolite, succinate, led to the rapid decline of intestinal CD8+ T cells but left systemic memory T cells unaffected. The purinergic receptor, P2RX7, is highly expressed by intestinal TRMs and chemical antagonism of this receptor markedly restored CD8+ T cells during succinate feeding. Using lymphocytic choriomeningitis virus (LCMV) infection to track antigen-specific CD8+ memory T cells, we found viral-specific CD8+ TRMs repopulate the intestine independent of LCMV reinfection after removal of succinate treatment. These findings highlight how commensal protists and their metabolites reset homeostatic CD8+ T cell carrying capacity through damage-independent stimulation of TRM apoptosis and regulate mucosal memory.
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Overall design |
6-week-old WT C56BL6/J mice were colonized with 1e6 T. mu or control (n=2 for control, n=5 for T. mu colonized). After 21 days, mice were sacrificed and the distal small intestine was excised. Intraepithelial CD8a+ T cells were sorted and pooled scRNA-seq was performed.
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Contributor(s) |
Nico KF, Raposo CJ, Satpathy AT, Howitt MR |
Citation missing |
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Submission date |
Jan 01, 2025 |
Last update date |
Jan 03, 2025 |
Contact name |
Colin J Raposo |
E-mail(s) |
craposo@stanford.edu
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Organization name |
Stanford University
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Department |
Pathology
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Lab |
Satpathy
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Street address |
240 Pasteur Drive, BMI 4600
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City |
Stanford |
State/province |
CA |
ZIP/Postal code |
94304 |
Country |
USA |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA1205369 |