Maturation of Innate Responses to Mycobacteria over the First Nine Months of Life
Bibliographic record
Abstract
Newborns and young infants are particularly susceptible to infections, including Mycobacterium tuberculosis. Further, immunogenicity of vaccines against tuberculosis and other infectious diseases appears suboptimal early in life compared with later in life. We hypothesized that developmental changes in innate immunity would underlie these observations. To determine the evolution of innate responses to mycobacteria early in life, whole blood or PBMC from newborns, as well as 10- and 36-wk-old infants, was incubated with viable Mycobacterium bovis bacillus Calmette-Guérin or TLR ligands. Innate cell expression of cytokines and maturation markers was assessed, as well as activation of the proinflammatory NF-κB- and MAPK-signaling pathways. Bacillus Calmette-Guérin-induced production of the proinflammatory cytokines TNF-α, IL-6, and IL-12p40 increased from the newborn period to 9 mo of age in monocytes but not in myeloid dendritic cells. No changes in production of anti-inflammatory IL-10 were observed. CD40 expression increased with age in both cell populations. Older infants displayed substantial activation of all three signal transduction molecules: degradation of NF-κB inhibitor IκBα and phosphorylation of MAPK Erk and p38 upon TLR1/2 triggering, compared with predominant activation of only one of any of these molecules in newborns. Maturation of innate proinflammatory responses during the first 9 mo of life may underlie more effective control of mycobacteria and other pathogens observed later in infancy and age-related differential induction of Th1 responses by vaccination.
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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 | 0.001 |
| 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".