Faculty Opinions recommendation of Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses.
Bibliographic record
Abstract
The lower intestine of adult mammals is densely colonized with non-pathogenic (commensal) microbes.Gut bacteria induce protective immune responses, which ensure host-microbial mutualism.The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics.Here we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation.A slow (>14 days) onset of a longlived (t1/2>16 weeks), highly specific anti-commensal IgA response in germ-free mice was observed.Ongoing commensal exposure in colonized mice rapidly abrogated this response.Sequential doses lacked a classical prime-boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.Immunoglobulin (Ig)A is the dominant antibody produced in mammals, mostly secreted across mucous membranes, especially in the intestine.Intestinal dendritic cells (DCs) sample small numbers of commensal bacteria at the mucosal surface and induce IgAproducing B cells through T cell-dependent and independent mechanisms (3-5).It has long been known that the IgA responses in the intestine are strongly induced by colonization of germ-free animals with commensal bacteria.The kinetics and longevity of these responses are unknown, however, because it has not been possible to uncouple IgA induction from constant bacterial exposure.We developed a reversible in vivo germ-free colonization system by studying the persistence of auxotrophic E. coli K-12 mutants with a requirement for essential nutrients that could not be satisfied by any mammalian host metabolites (fig.S1A).Initial experiments in which germ-free mice were gavaged with an asd deletion mutant deficient in meso-diaminopimelic acid (m-DAP) biosynthesis (6) resulted in persistent intestinal
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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 | 0.001 | 0.008 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.004 | 0.006 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.050 | 0.037 |
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".