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Neuroendocrine-immune interaction during inflammation - a phylogenetic study

Final Report Summary - NEUROINF (Neuroendocrine-immune interaction during inflammation - a phylogenetic study)

Project context and objectives

Neuroendocrine-immune interaction during inflammation - a phylogenetic study (NEUROINF)

It is now accepted that neuroendocrine pathways, e.g. triggered by stress signals, will have an impact on immunity and health just as the immune system may influence brain and endocrine functions. Indeed the neuroendocrine and immune systems are linked through bidirectional communication pathways that enable modification and coordination of physiological, behavioural and immunological responses upon changing internal and external conditions. This delicate balance between the neuroendocrine and immune systems is one of the most important factors conditioning homeostasis and, in consequence, animal health and welfare. Fish represent more than one half of all extant vertebrate species and their ability to continuously adapt to altered and altering circumstances by coordinated neuroendocrine and immune responses must have contributed to this success.

Project results

Neuroendocrine-immune interaction is based on a mutual language of signalling molecules and their receptors. Neural and endocrine cells are sensitive to immune stimuli (e.g. cytokines and chemokines) by expressing specific receptors for these. Vice versa the immune system can be modulated by expression of receptors specific for neurotransmitters and hormones on the leukocytes. The present project extended our knowledge about the mechanisms underlying protective immune responses in fish. We sequenced and characterised a carp adrenergic receptor (sensitive to the stress factor adrenaline) and showed that its gene is constitutively expressed not only in brain areas but also in immune organs (thymus, spleen) and in leukocytes. Moreover, its expression on leukocytes is regulated during an immune response. Additionally, we established the influence of adrenaline on the fish immune response. We found that although during inflammation adrenaline does not change the number of leukocytes in the focus of inflammation, it changes the leukocyte composition and influences their survival/apoptosis. Interestingly, adrenaline reduced the expression of mediators regulating cell migration (chemokines and their receptors), indicating changes in leukocyte recruitment after stress.

The project was also extended to study the effect of another neuroendocrine mediator - melatonin (hormone of darkness). We examined its effect on cell activity and apoptosis/necrosis. We found that similarly to mammals, in fish melatonin also works as a free oxygen radical scavenger and therefore promotes cell survival.

Furthermore, for a better fundamental understanding of factors involved in the regulation of inflammatory responses, we studied the involvement of chemokines in this process. We characterised in vitro and in vivo-specific subsets of carp chemokines (CXCLs) and their receptors (CXCR1-3). We showed that they are involved in inflammation where they regulate cell migration and activity.

Our data support the concept that neuroendocrine modulation may regulate inflammation to reach an optimum defense while preventing excessive host cell damage.

The results have been presented in six papers in peer reviewed scientific journals (four published, one in press, one submitted) and have been presented at international conferences.

Moreover, the project supported a complete reintegration of the fellow, Magdalena Chadzinska, within the host institute (Jagiellonian University, Krakow, Poland) and assured her job stability and professional independence as head of department. Additionally, the reintegration grant strengthened the successful and intensive collaboration with the Cell Biology and Immunology Group, Wageningen University (Netherlands), which was supported by Wagenigen Institute of Animal Sciences (WIAS) travel grants.

Currently, being fully reintegrated, Dr. Chadzinska has successfully submitted a new grant proposal to the Polish National Science Centre concerning interaction between stress susceptibility and immune response effectiveness in different carp lines.