Factors Regulating Murine Tuft cell Hyperplasia in the Small Intestine during Infection with <i>Hymenolepis Diminuta</i>
Bibliographic record
Abstract
Introduction At homeostasis, tuft cells form a rare epithelial cell population in the intestine. During parasitic infections with nematodes, the tuft cell has been shown to mobilize innate lymphoid type 2 cells (ILC2) by releasing the alarmin cytokine IL‐25. Enteric tuft cells possess key elements of the taste receptor pathway and may be luminal sensors of parasitic infections. Hymenolepis diminuta is a rat tapeworm that is rapidly expelled when introduced in immunocompetent murine hosts. During infection with this non‐abrasive, lumen dwelling parasite, immunocompetent mice display dramatic tuft cell hyperplasia across the small intestine. The factors regulating tuft cell response in this cestode model of infection are poorly understood. As observed in the nematode model of infection, we previously showed that tuft cell hyperplasia in response to H. diminuta is dependent on IL‐4 receptor mediated signalling. The influence of the adaptive immune system, which partakes in immunity against H. diminuta , was yet to be understood. Helminth infections are accompanied by alterations in the composition of the microbiota and may contribute to important luminal influences. Finally, it is poorly understood if tuft cell hyperplasia is regulated by changes in the sensory‐motor functions of the gut during helminth infection. Aims To test if mice lacking (1) a functional adaptive immune system, (2) a microbiome, and (3) TRPV1 + gut‐innervating sensory nerves display enteric tuft cell hyperplasia following infection with H. diminuta . Methods RAG‐1 −/− (male and female) and germ‐free mice (n=3–6) were orally gavaged with 5 cysticercoids of H. diminuta . Age matched non‐infected mice served as control groups. Male C57BL/6j mice (n=3–4) were treated with resiniferatoxin (RTX) to ablate TRPV1 + sensory neurons before infection. Mid‐jejunum cryosections (10mm) or paraffin embedded sections (5mm) were immuno‐stained against doublecortin‐like kinase ‐1 (DCLK‐1), a tuft cell marker, at 5, 8, 11 and 14 days post‐infection. Results Wild‐type C57BL/6j mice expel H. diminuta by 11 days post infection and display ~ 10–15 fold increase in tuft cells at this time. In RAG‐1 −/− mice, tuft cell hyperplasia at 11 days post‐infection was observed at a lesser magnitude than wild type mice. Germ‐free mice displayed tuft cell hyperplasia and kinetics of worm expulsion that were not different from wild‐type mice. RTX‐treated mice with confirmed loss of TRPV1 + nerve fibers in the gut and their cell soma in the dorsal root and nodose ganglia, had a greater increase (~2‐fold) in tuft cell numbers compared to the untreated infected wild‐type mice at day 11 post infection. Conclusion In the H. diminuta ‐ mouse model system, we find that tuft cell hyperplasia is largely, but not entirely dependent on adaptive immunity and occurs independent of the gut microbiota. The observation that TRPV1 + sensory nerves appear to contribute to regulation of tuft cell hyperplasia warrants further study on tuft cell‐sensory nerve interactions. Support or Funding Information NSERC, CIHR, Henry Koopman Memorial Entrance Scholarship in Gastrointestinal Nutrition, Metabolism and Inflammation
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".