Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

Abstract

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

Keywords: aryl hydrocarbon receptor; disease; environmental pollution; fish; halogenated aromatic hydrocarbons; immunity; immunotoxicity; polyaromatic hydrocarbons.

Figure 1

Adverse outcome pathway(s) for the immunotoxicity of AhR-activating xenobiotics. By binding to and activating the AhR as the molecular initiating event, xenobiotics potentially can dysregulate diverse molecular, cellular, and systemic key events in the immune system, and this eventually leads to compromised immunocompetence, impaired fitness (survival, reproduction), and to changes at the population level. Currently, the precise series of key events that link the molecular initiating event and the adverse outcomes is not known. Additionally, molecular initiating events alternative to AhR activation exist, which may mediate the immunotoxicity of AhR-activating xenobiotics. Still, the AOP framework can be instrumental to identify the knowledge gaps and direct future research on the immunotoxicity of AhR-activating xenobiotoics.