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Record W4318955550 · doi:10.1371/journal.ppat.1010884

A cercarial invadolysin interferes with the host immune response and facilitates infection establishment of Schistosoma mansoni

2023· article· en· W4318955550 on OpenAlexafffund
Jacob R. Hambrook, Patrick C. Hanington

Bibliographic record

VenuePLoS Pathogens · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicParasites and Host Interactions
Canadian institutionsUniversity of Alberta
FundersNatural Sciences and Engineering Research Council of CanadaUniversity of Alberta
KeywordsSchistosoma mansoniBiologyImmune systemImmunologyComplement systemProteasesInflammationSchistosomiasisHelminths

Abstract

fetched live from OpenAlex

Schistosoma mansoni employs immune evasion and immunosuppression to overcome immune responses mounted by its snail and human hosts. Myriad immunomodulating factors underlie this process, some of which are proteases. Here, we demonstrate that one protease, an invadolysin we have termed SmCI-1, is released from the acetabular glands of S. mansoni cercaria and is involved in creating an immunological milieu favorable for survival of the parasite. The presence of SmCI-1 in the cercarial stage of S. mansoni is released during transformation into the schistosomula. SmCI-1 functions as a metalloprotease with the capacity to cleave collagen type IV, gelatin and fibrinogen. Additionally, complement component C3b is cleaved by this protease, resulting in inhibition of the classical and alternative complement pathways. Using SmCI-1 knockdown cercariae, we demonstrate that SmCI-1 protects schistosomula from complement-mediated lysis in human plasma. We also assess the effect of SmCI-1 on cytokine release from human peripheral blood mononuclear cells, providing compelling evidence that SmCI-1 promotes an anti-inflammatory microenvironment by enhancing production of IL-10 and suppressing the production of inflammatory cytokines like IL-1B and IL-12p70 and those involved in eosinophil recruitment and activation, like Eotaxin-1 and IL-5. Finally, we utilize the SmCI-1 knockdown cercaria in a mouse model of infection, revealing a role for SmCI-1 in S. mansoni survival.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.742
Threshold uncertainty score0.330

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.019
GPT teacher head0.249
Teacher spread0.230 · 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; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations9
Published2023
Admission routes2
Has abstractyes

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