Understanding mechanisms of disease tolerance during intestinal helminth infection
Bibliographic record
Abstract
Abstract Intestinal helminths infect over two billion people worldwide and can cause significant morbidity. In many cases, however, individuals fail to develop resistance to these tissue-invasive pathogens, indicating that mammalian hosts have evolved unknown strategies to tolerate infection. To investigate the mechanisms underlying host tolerance to helminth infection, we examined the initial tissue invasive stage of Heligmosomoides polygyrus bakeri (Hpb), a natural parasitic roundworm infection of mice. Unexpectedly, we observed a rapid and robust Type 1 inflammatory response that preceded the expected Type 2 immune response. This early Type 1 response was associated with a gut-specific expansion of IFNγ-producing Eomesodermin+ Natural Killer (NK) cells with no increase in other innate lymphoid cell populations. Parabiosis and confocal microscopy studies indicated that Eomes+ NK cells are recruited from circulation and surround the larvae in association with the intestinal vasculature. The recruitment of NK cells to the small intestinal lamina propria is dependent on IFNγ-induced expression of CXCL9 and CXCL10, and the presence of αβ+ T cells. NK cell depletion did not alter worm burden or fitness, but resulted in increased incidence of intestinal bleeding, suggesting a role for NK cells in promoting intestinal vascular integrity. In summary, our work provides new insight into the cellular dynamics required for protection during intestinal helminth infection and will help inform strategies to maximize host fitness in the context of tissue injury and repair.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".