Th1 Cytokine Responses Fail to Effectively Control <i>Chlamydia</i> Lung Infection in ICOS Ligand Knockout Mice
Bibliographic record
Abstract
ICOS ligand (ICOSL) plays an important role in controlling specific aspects of T cell activation, differentiation, and function. Th1-type immune responses have been shown to be critical in host defense against chlamydial infections. To assess the role of ICOSL-ICOS interaction in host defense against chlamydial infection, we compared the immune responses and pathological reactions in ICOSL gene knockout (KO) and wild-type (WT) mice following Chlamydia muridarum lung infection. The results showed that ICOSL KO mice exhibited greater body weight loss, higher pathogen burden, and more severe histopathology in their lung than did WT mice. Cytokine analysis revealed that ICOSL KO mice produced lower levels of Th2 (IL-4 and IL-5) and anti-inflammatory (TGF-beta1 and IL-10) cytokines, but higher Th1-related (IFN-gamma and IL-12p40/IL-23) and proinflammatory (IL-6 and TNF-alpha) cytokines. ICOSL KO mice also showed reduced Chlamydia-specific Ab levels in their sera and lung homogenates. In addition, ICOSL KO mice demonstrated significantly lower ICOS expression in T cells and lower Th17 responses than did WT mice. Finally, we showed that ICOS-ICOSL interaction and cell-cell contact are essential for CD4(+) T cells to inhibit chlamydial growth in the cultured lung fibroblasts. The data suggest that ICOSL plays a significant role in immunoregulation and protective immunity against Chlamydia infections and that the Th1 skew in cytokine responses per se is not sufficient for effective control of Chlamydia infections.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".