NHR-49/PPARα regulates HLH-30/TFEB-mediated innate immune response via a flavincontaining monooxygenase in <i>C. elegans</i>
Bibliographic record
Abstract
Abstract The nematode C. elegans mounts an innate immune response against Gram-positive bacteria S. aureus by the transcriptional induction of multiple host defense genes. The expression of a majority of these genes is under the control of HLH-30, C. elegans homolog of TFEB (transcription factor EB) that also functions in the innate immune response in mammals. In addition to its role in host defense against S. aureus, HLH-30 acts as a nutritionally-controlled stress response factor. We wanted to deconvolve the response of C. elegans to nutritional challenge from the antibacterial response against S. aureus. To this end, we performed RNAseq profiling in wildtype and hlh-30 mutants that were either infected with S. aureus or were starved. Our RNAseq analysis showed that multiple HLH-30-dependent or-independent genes are specifically induced by S. aureus infection, and not by starvation. One of the genes that is highly induced by infection and not starvation is fmo-2, which encodes a member of the flavin-containing monooxygenase (FMO) family in C. elegans. We decided to characterize the role of FMO-2 in host defense in C. elegans by employing genetic, transgenic, and molecular approaches. We found that FMO-2 is important for host defense against S. aureus infection, and its induction during S. aureus infection is controlled by two transcription factors, HLH-30 and NHR-49 (C. elegans ortholog of the mammalian nuclear-hormone receptor, PPARα). Our results propose a model in which NHR-49 functions upstream of HLH-30 to bind to fmo-2 promoter and to induce its upregulation by functioning specifically in C. elegans intestine (the site of innate immune response), thereby providing host defense against S. aureus infection.
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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 | 0.000 | 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) | 0.002 | 0.001 |
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".