Caracterización molecular del reflejo inflamatorio y modulación de la respuesta inmune frente a infecciones en peces

Tesi d’estudis: Tesi doctoral

Resum

The inflammatory reflex is a neural circuit that modulates the innate immune system response preventing an overactivation. The first hypothesis of this thesis was to establish whether the inflammatory reflex described in mammals was also present in other vertebrates, and we focused on its study in Oncorhynchus mykiss. We cloned and characterised one of the main components of the inflammatory reflex: the alpha 7 nicotinic acetylcholine receptor (α7nAChR). The in vivo stimulation with LPS and poly (I:C) increased the receptor gene expression in different tissues and, also, modulated acetylcholine levels in plasma and spleen. The receptor was expressed in trout macrophages and was able to bind bungarotoxin, a specific receptor antagonist. Our results showed that nicotine modulates the gene expression of inflammatory genes in macrophages through α7nAChR after the stimulation with poly (I:C). In conclusion, the results provide evidences of evolutionary conservation of the inflammatory reflex in vertebrates. Teleost respond to an infections with the activation of a potent innate immune system aiming to eliminate pathogens. Thus, the modulation of the innate system would be an excellent target to improve the responsiveness of the fish to an infection. We have been used protein nanoparticles, known as inclusion bodies (IBs) as immunostimulants delivery platform. The IBs were efficiently internalized in vitro by both zebrafish hepatocytes (Danio rerio) and trout macrophages, and when IBs were administered in vivo they accumulated in the spleen and the head kidney of trout. Importantly, the IBs administered by intraperitoneal injection protect zebrafish against a lethal bacterial infection (Pseudomonas aeruginosa). The orally administered IBs were uptaken by cells of the intestinal mucosa. Our results suggest that the IBs could be an attractive alternative to stimulation of the innate immune system and can be administered orally overcoming the harsh conditions of the gastrointestinal tract.
Data del Ajut3 de juny 2016
Idioma originalEspanyol
Institució adjudicatària
  • Universitat de Barcelona (UB)
SupervisorNerea Roher Armentia (Director/a) & Simon Anthony Mackenzie (Director/a)

Keywords

  • Peixos
  • Infeccions
  • Resposta inmunitària

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