P1–165: Isolates of <i>Chlamydia pneumoniae</i> from the Alzheimer's brain infecting cultured human astrocytes and microglia display an active, not a persistent, growth phenotype
Bibliographic record
Abstract
The intracellular bacterial pathogen C pneumoniae can cause persistent infections, during which its pathogenic characteristics differ from those of active infection. This organism was identified in astrocytes and microglia in the late–onset Alzheimer's disease (AD) brain. We cultured this organism from AD brain samples from two North American locations. Because the mechanisms of pathogenesis differ between active and persistent infection, we asked whether infection of the two common human CNS host cell types with the brain isolates displays an active or persistent phenotype. The human astrocytoma and microglioma cell lines U–87 MG and CHME–5 (respectively), and the human epithelial line HEp–2, were infected at MOI 1:1 with C pneumoniae index strain AR–39 as control, and with the Tor–1 (from a Toronto sample) and the Phi–1 (from a Philadelphia sample) AD brain isolates. Cultures were harvested at 24, 48, and 72 hr post–infection and subjected to analyses of inclusion number, size, morphology, and recovery of new organisms. DNA/RNA were prepared from infected cultures and analyzed for chromosome accumulation and presence/absence of specific bacterial mRNAs. Glial cells infected with C pneumoniae of the control strain and with both brain–derived isolates displayed inclusions indistinguishable from those characteristic of active infection of standard HEp–2 host cells. Real time PCR showed that accumulation of chlamydial DNA over time during infection of the two glial cell lines was similar to that in actively–infected HEp–2 cells. RT–PCR showed that mRNA from ftsK, pyk, and other chlamydial genes whose expression is attenuated during persistent infection were easily identifiable in Tor–1 and Phi–1 infected CHME–5 and U–87 MG cells. Recovery of new organisms at the termination of the chlamydial developmental cycle was equivalent for the AR–39 control–infected U87 and CHME–5 cells, and for those cells infected with the Tor–1 and Phi–1 brain isolates. In cultured human astrocytes and microglia, C pneumoniae isolated from the AD brain displays an active, rather than a persistent, growth phenotype. This observation indicates normal passage through the developmental cycle, demonstrating the destruction by lysis of some portion of host cells at the termination of that cycle in the CNS.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".