Clathrin‐mediated phagosome resolution regenerates lysosomes and maintains degradative capacity of macrophages after phagocytosis
Bibliographic record
Abstract
Phagocytosis is the selective internalization of large particles and is critical for immunity, development and tissue homeostasis. The conversion of phagosomes into microbicidal compartments is a highly regulated process, which has been studied in great detail. Conversely, the fate of phagolysosomes, after their cargo is digested, is poorly understood. By utilizing fluorescent bacteria and labelling phagosomal markers, we followed mature phagolysosomes to their resolution. Despite previous assumptions, phagolysosomes are not exocytosed, but instead undergo a continuous dismembering process resulting in the shedding of myriads of vesicles containing degraded cargo. These phagosome‐derived vesicles resemble lysosomes, based on the acquisition of lysosomal markers, acidification and fusogenicity with newly formed phagosomes. Combining pharmacological and genetic strategies, we found that phagosomal fragmentation is dependent on cargo degradation, clathrin and the integrity of the actin and microtubule cytoskeleton. In addition, we provide evidence that phagosome‐derived vesicles are required to recycle lysosomal components allowing for the formation of new phagosomes and consequently maintaining the capacity of macrophages to ingest targets. Thus, we propose that phagolysosome resolution recycles cellular resources for the continuous generation of new phagosomes and the prevention of this phase will critically impair the immune and housekeeping functions of the phagocytes. Support or Funding Information Canadian Institutes of Health Research Canada Research Chairs Program Ryerson University Natural Sciences and Engineering Council of Canada Clathrin mediates phagosome resolution. A. Macrophages engulfed mRFP1‐expressing E. coli. At 1 h post‐phagocytosis, phagosomes are rod‐shaped, like E. coli and mRFP1 is mostly associated with phagosomes. After 4 h of phagosome maturation, phagosomes shrunk and mRFP1 is found in small vesicular compartments. Clathrin inhibitors, pitstop and ikarugamycin, impair phagosome fragmentation. B. Quantification of phagosome‐derived vesicles, where b is significantly different from other conditions. Figure 1
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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".