Polygenic <scp>TB</scp> control and the sequence of innate/adaptive immune responses to infection: <scp>MHC</scp>‐<scp>II</scp> alleles determine the size of the <scp>S100A8</scp>/9‐producing neutrophil population
Bibliographic record
Abstract
Abstract Among several quantitative trait loci involved in tuberculosis (TB) control in mice, one was mapped within the chromosome 17 segment occupied by the H2 complex and another within the chromosome 3 segment comprising the S100A8/9 genes, which encode neutrophil inflammatory factor S100A8/9. Previously, we developed a panel of H2‐congenic mouse strains differing by small segments of the major histocompatibility complex Class II (MHC‐II) region from TB‐susceptible H2j mice transferred onto the genetic background of the TB‐resistant C57BL/6 (H2b) strain. Susceptible B6.I‐9.3 mice differ from B6 progenitors by the alleles of their only classical MHC‐II H2‐Aβ gene. The goals of the present study were to: (i) comprehensively characterise the differences in TB‐related phenotypes between mice of the two strains and (ii) decipher interactions between the H2‐Aβ and S100A8/9 genes. Here, we describe the dynamics of TB‐related phenotypes differentiating B6.I‐9.3 and B6 mice (colony forming units counts, histopathology, lung immune cell infiltration and cytokine profiles). We show that disproportionally diminished CD4+ T‐cell population, an enlarged S100A8/9‐positive neutrophil population and higher S100A8/9 serum levels in B6.I‐9.3 mice collectively form the ‘susceptible’ phenotype before infection. An increase in IL‐17 and a decrease in intrferon‐gamma production by CD4+ T‐cells in these mice provide a mechanistic explanation of this phenotype. Using F2 segregation analysis, we show that the number of S100A8/9‐producing neutrophils in lungs and spleens and the proportion of Th17 CD4+ T‐cells in lungs are significantly lower in the presence of the MHC‐II dominant ‘resistant’ b allele compared to the recessive ‘susceptible’ j/j genotype. This provides direct genetic evidence that MHC‐II‐regulated CD4+ T‐cell landscapes determine neutrophil abundance before infection, an important pathogenic factor in TB immunity.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
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".