Decoding innate immune signatures driving trained and adaptive immunity in fish using a high-resolution in vivo and in vitro zebrafish model
By Louise von Gersdorff Jørgensen
By utilizing an in vivo zebrafish model, we can decode the nature of the innate responses on a cellular level and predict the nature of trained and acquired protection.
SUMMARY AND AIM:
Fish rely heavily on their innate immune system for protection against pathogens. Nevertheless, immunological protection can also be achieved through natural infections or vaccination. For a vaccine to induce durable adaptive protection, activation of innate immunity is required to initiate and shape immune memory. Recent studies have provided initial evidence of trained immunity in fish, a form of innate memory mediated by epigenetic and metabolic reprogramming of innate immune cells. However, the molecular underpinnings, duration, and functional relevance of trained immunity in fish remain poorly defined. To address these knowledge gaps, we will decode innate immune signatures that drive the induction of trained and adaptive immunity in zebrafish (Danio rerio, zf). Specifically, we will investigate whether the stimuli promoting adaptive immunity overlap with, or differ from, those that trigger trained responses.
| Hypothesis: Biomarkers of innate immune activation, that lead to trained and/or adaptive immunity, depend on the nature of the antigen. |
To test this, we will employ complementary in vivo and in vitro zf approaches to analyse the magnitude and quality of neutrophil and macrophage effector mechanisms, as well as their transcriptional programs, in response to distinct parasitic Ichthyophthirius multifiliis (Ich) and bacterial Vibrio anguillarum (Va) antigens. Aim: To investigate how zf neutrophils and macrophages integrate different antigenic signals to initiate trained and adaptive immunity, with the goal of identifying biomarkers that predict the induction and modulation of long-term protective responses.
PLANNED WORKS:
COLLABORATORS:
- Philip Elks, Sheffield University
- Mikolaj Adamek, University of Hannover
- Louise Kruse Jensen, University of Copenhagen
FUNDING:
The project is funded by Danmarks Frie Forskningsfond