Cutaneous Infection with <i>Leishmania major</i> Mediates Heterologous Protection against Visceral Infection with <i>Leishmania infantum</i>
Bibliographic record
Abstract
Visceral leishmaniasis (VL) is a fatal disease of the internal organs caused by the eukaryotic parasite Leishmania. Control of VL would best be achieved through vaccination. However, this has proven to be difficult partly because the correlates of protective immunity are not fully understood. In contrast, protective immunity against nonfatal cutaneous leishmaniasis (CL) is well defined and mediated by rapidly recruited, IFN-γ-producing Ly6C(+)CD4(+) T cells at the dermal challenge site. Protection against CL is best achieved by prior infection or live vaccination with Leishmania major, termed leishmanization. A long-standing question is whether prior CL or leishmanization can protect against VL. Employing an intradermal challenge model in mice, we report that cutaneous infection with Leishmania major provides heterologous protection against visceral infection with Leishmania infantum. Protection was associated with a robust CD4(+) T cell response at the dermal challenge site and in the viscera. In vivo labeling of circulating cells revealed that increased frequencies of IFN-γ(+)CD4(+) T cells at sites of infection are due to recruitment or retention of cells in the tissue, rather than increased numbers of cells trapped in the vasculature. Shortly after challenge, IFN-γ-producing cells were highly enriched for Ly6C(+)T-bet(+) cells in the viscera. Surprisingly, this heterologous immunity was superior to homologous immunity mediated by prior infection with L. infantum. Our observations demonstrate a common mechanism of protection against different clinical forms of leishmaniasis. The efficacy of leishmanization against VL may warrant the introduction of the practice in VL endemic areas or during outbreaks of disease.
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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 | 0.000 |
| 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 | 0.001 |
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".