Intestinal Mucosal Immunology of Salmonids Response to Stress and Infection and Crosstalk with the Physical Barrier

Abstract

The effect of environmental factors and pathogens on the intestinal epithelium of fish has received increased attention in recent years. Studies focusing on effects of stress, nutrient uptake as well as vegetable ingredients in fish feed have all shown that the intestine is affected by environmental factors. The signs of inflammation during exposure to detrimental environmental conditions have brought to attention the local immune system in the gut. The gut is further one of the main routes for pathogen infection in fish. Therefore this thesis aims at investigating the mucosal immune factors and systems that are affected by environmental stressors and pathogen interactions.

In this thesis the effect of long term environmental stress on the mucosal intestinal epithelium was investigated. Results showed an ongoing inflammation in the intestine that was manifested as a compromised barrier integrity, infiltration of immune cells and an affected immune response. Atlantic salmon was co-habitant infected with infectious pancreatic necrosis virus as well as immune challenged with the viral mimicker, double stranded RNA Poly I:C, where after the mucosal immune response was studied. Both treatments clearly demonstrated an antiviral response including alterations of IFN type I and the Mx protein. When the fish were exposed to a stressor and immune stimulation in combination, the fish immune response was delayed. This stresses the importance of minimize stressful situations for the animals in, for example aquaculture. The demonstrated increase in intestinal epithelial permeability together with inductions of the mucosal immune system raises the question of whether stress or inflammation is the causative agent of the barrier dysfunction.

To address this, the effect of the immune system on the intestinal epithelia was assessed using an in vitro Ussing chamber approach in which the intestinal epithelia was exposed to recombinant cytokines. Exposure to IL-1β and IL-6 showed negative impact on the intestinal permeability, suggesting that the immune system of the fish is contributing to the inflammation seen during prolonged stress. Further, the tight junction proteins create an extracellular net-work between the epithelial cells and by that controls the intestinal paracellular permeability was shown to be affected by the two cytokines. The interactions between stress, the immune system and the epithelial barrier function are therefore highly complex and important for our understanding of the physiology of health, welfare and disease.