Dexamethasone modulates expression of genes involved in the innate immune system, growth and stress and increases susceptibility to bacterial disease in Senegalese sole (Solea senegalensis Kaup, 1858)

Abstract

Cortisol, the main glucocorticoid in fish, undertakes pleiotropic biological effects in response to stressors to maintain homeostasis. It can exert several actions on the immune system, growth and cellular metabolism, establishing a fine-tune regulation stress response and cross-talk interactions with other regulatory pathways. In this study, we investigated a causal relationship between high levels of glucocorticoids and susceptibility to pathogens and modification of gene expression profiles in Senegalese sole. For this purpose, we carried out two experiments using post-metamorphic individuals (21 days after hatching) that were exposed to dexamethasone (DXM), a potent glucocorticoid, in order to mimic cortisol effects. We quantified transcript levels of a wide set of genes involved in innate immune system (g-type lysozyme and hepcidin (hamp1)), HPI axis (crf, crfbp, pomcα, pomcβ, gr1 and gr2), HPT axis (tgb), cellular stress defense system (hsp70 and hsp90aa), GH/IGF axis (igf-I and igf-Ir) and the neuropeptide trh. Short-term exposure to 0.1, 1 and 10 ppm DXM provoked a reduction of pomcβ transcripts and an increase of crfbp mRNAs in a dose-dependent manner at 48 and 72 h after treatment. Moreover, g-type lysozyme transcript levels decreased significantly at 72 h whereas hamp1 mRNA levels increased at 48 h after exposure. Long-term DXM treatment (10 ppm DXM) affected negatively weight of soles (∼20% lower than controls). Moreover, reduced mRNA levels were observed for pomcβ after 1 week and igf-I and hamp1 after 2 weeks. In contrast, crfbp and crf increased mRNA levels after 2 weeks. hsp70 exhibited a dual response increasing transcript levels at 1 week after treatment and reducing thereafter. No significant changes in gene expression were observed at any time during this study for tgb, trh, hsp90aa, pomcα, gr1 and gr2. Finally, a challenge experiment using the pathogen Photobacterium damselae subsp piscicida confirmed earlier and higher mortalities in DXM-treated animals. Taken together, these data indicate that a prolonged exposure to DXM increases the susceptibility to pathogens and reduces growth. Moreover, DXM can trigger a wide cellular response modulating the expression of genes involved in the innate immune system, HPI and GH/IGF axes as well as cellular stress defense. These results are highly valuable to evaluate responses associated to aquaculture stressful conditions and discriminate specific glucocorticoid-mediated effects.