<i>Cryptococcus</i> displays spore-specific uptake by alveolar epithelial cells
Bibliographic record
Abstract
ABSTRACT Human fungal pathogens, including Cryptococcus neoformans, cause 1.5 million annual deaths. Cryptococcus causes disease when it disseminates out of the lung and into the brain, which can occur years after initial exposure (latency) via mechanisms that remain unknown. Spores of Cryptococcus display distinct surface epitopes, host interactions, and disease kinetics to the vegetatively growing yeast morphotype, yet they remain understudied, likely contributing to our lack of understanding of pathogenesis. One of the first barriers spores encounter is non-professional phagocytic a irway e pithelial c ells (AECs). Here, we demonstrate that Cryptococcus spores are preferentially internalized by AECs both in vitro and in vivo . Once inside, spores can germinate, subsequently replicate, persist, and/or escape. This ability to enter AECs correlates with a preferential ability of spores to cross AEC barriers. Together, our work indicates that AECs internalize Cryptococcus spores and may serve as a previously ignored intracellular host niche, providing alternative hypotheses for both Cryptococcus dissemination and latency. IMPORTANCE Fungal spores are a dormant, stress-resistant, and relatively understudied cell type and are presumed infectious cell types in cryptococcal disease. Cryptococcus spores have been shown to display distinct disease kinetics to the vegetative yeast morphotype and are significantly better at disseminating out of the host lung. While the molecular mechanisms by which spores disseminate out of the lung have yet to be identified, their preferential ability to get inside host cells likely enables their dissemination. Here, we show that spores, unlike yeast, readily get taken up by non-professional phagocytic cells, airway epithelial cells, both in vitro and in vivo, and once inside can germinate, replicate, escape, and/or persist. These results provide a previously unexplored host cell type that Cryptococcus can inhabit, likely affecting disease kinetics and could be a critical interaction in understanding both extrapulmonary dissemination and latency.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".