eLife Assessment: Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
Bibliographic record
Abstract
Despite their superficial similarities, the phagocytosis of pathogens differs from that of apoptotic cells in their recognition mechanisms and downstream signaling pathways. While the initial stages of these processes have been studied, the cytoskeletal reorganization that follows particle uptake is not well understood. By comparing the uptake of phosphatidylserine (PS)- coated targets versus IgG-opsonized targets of identical size, shape, and rigidity, we noted remarkable differences in the accompanying changes in cell morphology, adhesion and migration that persisted long after phagocytosis. While myeloid cells continued to survey their microenvironment after engulfing PS-coated targets, the uptake of IgG-opsonized targets caused phagocytes to round up, decreased their membrane ruffling, and led to the complete disassembly of podosomes. These changes were associated with increased activation of Rho and a concomitant decrease of Rac activity that collectively resulted in the thickening and compaction of the cortical F-actin cytoskeleton. Rho/formin-induced actin polymers were fastened to the membrane by their preferential interaction with Ezrin-Radixin-Moesin (ERM) proteins, which were necessary for cell compaction and podosome disassembly following ingestion of IgG-coated particles. The source of the distinct responses to PS- versus IgG-targets was the differential activation of the respiratory burst mediated by the NADPH oxidase: reactive oxygen species (ROS), emanating from phagosomes containing IgG-opsonized targets – but not those containing PS-coated ones – directly led to the activation of Rho. Similar findings were made with phagocytes that encountered pathogens or microbial-associated molecular patterns (MAMPS) that instigate the activation of the NADPH oxidase. These results implicate a connection between sensing of harmful particulates, the oxidation of cytoskeletal regulators, and the immune surveillance by myeloid cells that have potentially important consequences for the containment of pathogens.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.043 | 0.014 |
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 source (direct Gemma or distilled Codex), 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".