In vitro characterization of granulocyte-colony stimulating factor (G-CSF) production by dendritic cells and macrophages during Streptococcus suis infection
Bibliographic record
Abstract
Streptococcus suis serotype 2 is an important porcine bacterial pathogen and emerging zoonotic agent. Infections induce an exacerbated inflammation that can result in sudden death (septic shock) and meningitis. Though neutrophilic leukocytosis characterizes S. suis infection, the mediators involved are poorly understood. Among them, granulocyte-colony stimulating factor (G-CSF), a pro-inflammatory cytokine, triggers proliferation of neutrophil progenitors and neutrophil mobilization. However, the systemic production of G-CSF induced during S. suis infection, the cell types involved, and the underlying mechanisms remain unknown. In a S. suis serotype 2 mouse model of systemic infection, plasma levels of G-CSF rapidly increased after infection. S. suis activation of DCs and macrophages resulted in high (> 1000 pg/mL) and comparable production levels of G-CSF, as measured by ELISA. By using mutant strains deficient in capsular polysaccharide (CPS) or lipoprotein maturation in combination with purified lipoteichoic acid (LTA) from the latter mutant strain, it was showed that G-CSF production is mainly mediated by S. suis lipoproteins. The Toll-like receptor (TLR) pathway via myeloid differentiation primary response 88 (MyD88) is required for G-CSF production by DCs and macrophages following S. suis activation, with a partial involvement of TLR2. On the other hand, TLR2-independant G-CSF production induced by S. suis requires internalization and bacterial DNA might play a role in this pathway. Finally, these signals activated nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways leading to G-CSF production. In conclusion, this study demonstrated for the first time that S. suis induces G-CSF production in vivo and DCs and macrophages are key cellular sources of this cytokine mediator, mainly via the binding of lipoproteins to TLR2. The CPS significantly reduced this activation, confirming the powerful role of this component in S. suis virulence. As such, this study contributes to better understand how DCs and macrophages produce G-CSF in response to S. suis, and potentially to other streptococci.
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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) | 0.001 | 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 | 0.001 |
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".