The transcriptional analysis of the macrophages' innate immune responses to «Salmonella typhiumurium and Legionella pneumophila» infection
Bibliographic record
Abstract
Macrophages are the first line of defense against microbial pathogens; they recognize microbial structures and products via surface receptors (Fc, C3b, SR, TLR) and intracellular antigen sensors (NLR family). Engagement of surface receptors results in phagocytosis of the microbe into a specialized vacuole, the phagosome. Through a series of fusogenic events, the phagosome matures into a fully microbicidal phagolysosome that is highly acidic and contains a number of degradative enzymes and toxic molecules that cause destruction of the microbe. Salmonella typhimurium (S. typhimurium) and Legionella pneumophila (L. pneumophila) are two pathogenic Gram-negative bacteria that are able to block phagosome maturation. Our hypothesis is that the macrophages' response to these pathogens contains a core response, which is induced by both pathogens, as well as a pathogen-specific response. We used a genome-wide transcription profiling approach to compare macrophage responses to phagocytosis of S. typhimurium or L. pneumophila at early time points, 2h (T2) and 4h (T4) post-infection (p.i.). The infections were performed on the macrophage-like cell line J774, and RNA isolated from infected and non-infected cells was hybridized to Mouse WG6 Illumina microarrays. Pairwise analysis led to the identification of 159 genes differently regulated compared to Non Infected (NI) samples in response to L. pneumophila infection at T2, 148 genes at T4 and 192 genes differently regulated in response to S. typhimurium at T2, and 402 genes at T4. Comparative analysis identified three groups of genes: 164 (T2) and 347 (T4) "Salmonella typhimurium-specific" genes, 131 (T2) and 99 (T4) "Legionella pneumophila-specific" genes. This analysis also revealed that 28 (T2) and 49 (T4) genes were differentially expressed in response to both pathogens. A list of 27 genes was validated using quantitative RT-PCR. Networking programs, including STRING or Pathvisio were used to generate 3 interaction networks illustrative of these three groups of genes. Our results clearly show that TNF-α is associated with the macrophage response to both infections, with this gene playing a central role in this pathway. The Legionella specific pathway is centered on Egr1, Fos and Jun whereas the Salmonella specific pathway has 3 nodes centered on Il10, Il6 and Ccnd1.
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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) | 0.001 | 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 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".