NK and NKT Cell-Independent Contribution of Interleukin-15 to Innate Protection against Mucosal Viral Infection
Bibliographic record
Abstract
Interleukin-15 (IL-15) is essential for the development, maturation, and function of NK and NKT cells, which are critical components of the innate immune defense against viral infections. We recently showed that mice lacking IL-15 and/or NK/NKT cells are significantly more susceptible to intravaginal (IVAG) herpes simplex virus type 2 (HSV-2) infection than control mice. For this study, we examined whether IL-15 has any direct antiviral activity, independent of NK/NKT cells, in innate protection against HSV-2 infection. A sensitive enzyme-linked immunosorbent assay for murine IL-15 was developed and used to show that IVAG HSV-2 infection induces IL-15 in vaginal washes. Using immunohistochemistry, we detected IL-15-positive cells in the submucosa and vaginal epithelium following IVAG HSV-2 infection. Local, but not systemic, delivery of murine recombinant IL-15 (mrIL-15) to the genital mucosae of IL-15(-/-) and RAG-2(-/-) gamma(c)(-/-) mice, which both lack NK and NKT cells, resulted in significant reductions in HSV-2 titers in genital washes and 60% survival following IVAG HSV-2 challenge. Furthermore, we showed that IL-15 is important for CpG oligodeoxynucleotide (ODN)-induced innate protection against genital HSV-2 infection. While 100% of CpG ODN-treated RAG2(-/-) gamma(c)(-/-) mice, which are capable of producing IL-15 but lack NK/NKT cells, survived an IVAG HSV-2 challenge, only 60% of CpG ODN-treated IL-15(-/-) mice survived, and all of these mice had similar vaginal viral titers to those in control mice by day 3 postchallenge. Lastly, a treatment of RAW264.7 cells with mrIL-15 induced the production of tumor necrosis factor alpha and beta interferon (IFN-beta), but not IFN-alpha, and significantly protected them against HSV-2 infection in vitro. The results of these studies indicate that IL-15 can act independently of NK/NKT cells in mediating the innate defense against viral infection.
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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) | 0.001 | 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".