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Series GSE285649 Query DataSets for GSE285649
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
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.
 
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.
 
Contributor(s) Nico KF, Raposo CJ, Satpathy AT, Howitt MR
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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
Organization name Stanford University
Department Pathology
Lab Satpathy
Street address 240 Pasteur Drive, BMI 4600
City Stanford
State/province CA
ZIP/Postal code 94304
Country USA
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (2)
GSM8706348 CD8pos_SPF
GSM8706349 CD8pos_TmuColonized
Relations
BioProject PRJNA1205369

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Supplementary file Size Download File type/resource
GSE285649_RAW.tar 49.6 Mb (http)(custom) TAR (of H5)
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Raw data are available in SRA

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