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C3 complement mediates neutrophil control of cryptococcal lung infection and dissemination

2020· article· en· W4313368581 on OpenAlexaff
Henry Ogbomo, Shu Shun Li, Danuta Stack, Andrew Chojnacki, Katarzyna Wójcik, Maria J. Polyak, Pina Colarusso, Paul Kubes, Christopher H. Mody

Bibliographic record

VenueThe Journal of Immunology · 2020
Typearticle
Languageen
FieldMedicine
TopicFungal Infections and Studies
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsCryptococcus neoformansPhagocytosisBiologyCryptococcosisLungMicrobiologyImmune systemInnate immune systemImmunologyComplement systemMedicine

Abstract

fetched live from OpenAlex

Abstract The encapsulated budding yeast Cryptococcus neoformans causes meningitis and pneumonia particularly in immunocompromised individuals including HIV-infected patients. The organism is acquired by the pulmonary route where it disseminates via the bloodstream from the lung to the brain and causes meningitis. Since the lung vasculature is replete with several innate immune cells, it is conceivable that the host would mount an immune response in the pulmonary vasculature to prevent or at least limit the dissemination of C. neoformans to other sites of the body. Hence, we used intravital microscopy to study the host cell immune interactions that occur within the lung vasculature in a living mouse. We found that neutrophils, but not monocytes, interacted with and phagocytosed C. neoformans. Interestingly, additional neutrophils underwent accretion around the phagocytosed C. neoformans, forming a cast of the vasculature. Phagocytosis of C. neoformans was impaired by the presence of cryptococcal capsule, since acapsular strain of C. neoformans were rapidly phagocytosed by neutrophils compared with encapsulated strain. Neutrophil phagocytosis of C. neoformans and subsequent accretion was mediated by complement C3 in both acapsular and encapsulated strains. Mice deficient in C3 complement showed reduced clearance of C. neoformans from the lungs and brain, compared to C3 sufficient mice. These findings highlight the importance of neutrophils in the control of C. neoformans in the pulmonary vasculature and subsequent dissemination to the distal organs including the brain.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
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 score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

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)0.0010.000

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 head0.014
GPT teacher head0.286
Teacher spread0.272 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2020
Admission routes1
Has abstractyes

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