Neuroendocrine-immune interaction and its implication for immunity in teleost fish

Stress and Immune Regulation

It is now recognized that the neuroendocrine- and immune systems interact in a bi-directional fashion. In this way the status of  pathogen recognition is communicated to the brain and the immune response is influenced by physiological changes. This explicit communication consequently needs a common language of signaling molecules and receptors. The network includes corticosteroids, classical pituitary hormones, cytokines and neuropeptides, as well as neural pathways. Understanding the basic biological significance of this dialogue may provide therapeutic benefit for treatment of pathologies. We focus on the pathways, receptors and mechanisms involved in teleost fish which form an excellent model to reveal phylogenetically old and original mechanisms of stress physiology and immunology.

Recent sequencing of several fish interleukins and studies to their expression, and their regulation through neuroendocrine factors like cortisol, provide evidence for a mutual influence and coordinate action of both systems. In aquaculture procedures, where stressful circumstances of crowding and handling are inevitable, changes in Hypothalamus-Pituitary-Interrenal (HPI)-axis hormones may have serious impact on immune functioning. This is studied in carp in acute or chronic stress paradigms and differential sensitivity to cortisol and POMC- peptides was determined. The different gluco and minaeral corticoid receptor genes (GR and MR) and their splice variants are studied in carp and are all differentially expressed in vivo and show different affinity for their ligand in vitro. Hereby teleostean fishes can be seen as model species, with different functional GR proteins within one organism, which ennables investigation of the molecular basis of cortisol resistance.

Opioids peptides and their role in immune defense

Opioids can affect the immune response either directly via opioid receptors localised on leukocytes, or indirectly via activation of stress axis and sympathethic nervous system. We identified opioid  and receptors have been identified in fish and their evolutionary relationship with mammalian factors and functions supports their essential role in neuroendocrine and immune responses. This project is a collaboration with the Jagiellonian University in Krakau Poland (granted by EU, Magda Chadzinska) and aims to undertake a joint effort within three laboratories to perform an interdisciplinary study into the role of opioids and opioid receptors in farmed fish.

Cytokine regulation of innate immunity in teleost fish

Cytokines are important regulators of inflammatory responses. Also within the teleost immune sytem, cytokines are rapidly identified and we are beginning to understand their physiological importance for immunological defence. Their low level of evolutionary conservation, their pleiotropic nature and redundancy illustrates the complexity, but molecular characterization of several important inflammatory cytokines could be achieved and recombinant proteins are available. Our focus at this moment is directed towards the pro-inflammatory cytokines of the IL-1 family, Tumour Necrosis Factor (TNF, see G. Wiegertjes), Interferon, and the different chemokine families as well as the anti-inflammatory cytokines. A genome-wide approach of database mining at this moment allows characterization of the complete profile of cytokines in teleosts and moreover provides new insight into their phylogenetic origin.

Modulation of Immune Response through Low Frequency Electromagnetic Field (LF EMF) exposure

In vitro and in vivo studies with animals provide evidence that properly selected electromagnetic fields (EMF) have protective effects against infections by activating the immune system. A remarkable finding is that such effects can be obtained at very low field strengths: from 50 μT down to at least 1 μT.
The goal of the current project is to explore hazards and benefits related to immune system activity of low frequency (LF) EMF exposure that may help understand and even predict health effects of such exposure. Studies are performed with different species within an international collaborative setting.

Post Doc and PhD projects

• Dr. Magda Chadzinska. The role of opioids in protective immune responses of carp
• Drs. Lieke Golbach. Modulation of Immune Response through Low Frequency Electromagnetic Field (LF EMF) exposure