CD154 restricts helminth-induced macrophage polarization and proliferation while promoting tissue residence
Why this work is in the frame
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Bibliographic record
Abstract
CD154 (CD40L) is of central importance in effector responses mediated by classically activated macrophages. However, there is limited information on the impact of CD154 on macrophage responses in type 2 contexts, characterized by IL-4-induced polarization and proliferation. CD154 restricts the polarization and proliferation of peritoneal cavity macrophages in response to exogenous IL-4. Here we address the impact of CD154 on peritoneal macrophages during infection of mice with the intestinal helminth Heligmosomoides polygyrus. This strictly enteric nematode causes recruitment of Th2 cells and macrophages to the peritoneal cavity alongside type 2 polarization and proliferation of recruited and resident macrophages. Nine days post-infection, there was an increase in the expression of cell-surface CD154 in CD4 + T cells together with increased IL-13 levels in the cavity, suggestive of local antigen presentation. Blocking CD154 enhanced the proliferation of resident but not of recently recruited macrophages. CD154 blocking additionally potentiated the expression of type 2 marker Ym1 ( Chil3 ) in resident and recruited macrophages. Unexpectedly, CD154 blocking caused increases in the numbers of recently recruited macrophages and appearance of cells with characteristics of both differentiating recruited macrophages (expression of folate receptor β and MHCII) and resident macrophages (high-level expression of F4/80 and CD102). Together, these observations suggest that CD154 promotes the acquisition of tissue residence by recruited macrophages. Thus, our results indicate that in a helminth infection CD154 restricts certain aspects of the polarization and proliferation of macrophages in response to type 2 cytokines while promoting the acquisition of resident phenotype by the recruited macrophages.
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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 it