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Record W4392907173 · doi:10.1016/j.mucimm.2024.03.003

Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8+ T cell responses

2024· article· en· W4392907173 on OpenAlexfundno aff
Breanne E. Haskins, Jodi A. Gullicksrud, Bethan A. Wallbank, Jennifer E. Dumaine, Amandine Guérin, Ian S. Cohn, Keenan M. O’Dea, Ryan D. Pardy, Maria Merolle, Lindsey A. Shallberg, Emma N Hunter, Jessica H. Byerly, Eleanor J. Smith, Gracyn Y. Buenconsejo, Briana McLeod, David A. Christian, Boris Striepen, Christopher A. Hunter

Bibliographic record

VenueMucosal Immunology · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicParasitic Infections and Diagnostics
Canadian institutionsnot available
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchEuropean Molecular Biology OrganizationLouisiana Academy of SciencesNational Institutes of HealthNational Institute of Allergy and Infectious DiseasesCommonwealth of Pennsylvania
KeywordsEffectorCryptosporidiumCell mediated immunityParasite hostingBiologyDendritic cellCellImmunologyImmunityCD8Cell biologyT cellMicrobiologyImmune systemGenetics

Abstract

fetched live from OpenAlex

Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function . However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, Cryptosporidium was engineered to express a parasite effector protein (MEDLE-2) that contains the major histocompatibility complex-I restricted SIINFEKL epitope which is recognized by T cell receptor transgenic OT-I(OVA-TCR-I) clusters of differentiation (CD)8 + T cells. These modified parasites induced expansion of endogenous SIINFEKL-specific and OT-I CD8 + T cells that were a source of interferon-gamma (IFN-γ) that could restrict growth of Cryptosporidium . This T cell response was dependent on the translocation of the effector and similar results were observed with another secreted parasite effector (rhoptry protein 1). Although infection and these translocated effector proteins are restricted to intestinal epithelial cells, type 1 conventional dendritic cells were required to generate CD8 + T cell responses to these model antigens. These data sets highlight Cryptosporidium effectors as potential targets of the immune system and suggest that crosstalk between enterocytes and type 1 conventional dendritic cells is crucial for CD8 + T cell responses to Cryptosporidium .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.354
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.019

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.

Opus teacher head0.012
GPT teacher head0.259
Teacher spread0.247 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; both teacher heads agree on what is shown here.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations13
Published2024
Admission routes1
Has abstractyes

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