Early Life Glucocorticoid Exposure Modulates Immune Function in Zebrafish (Danio rerio) Larvae

Frontiers in Immunology

Marcel Schaaf¹  Robert Whelan¹  Suzanne Cromwijk²  Ruud van den Bos²  Joep Althuizen²  Jan Zethof²  Katharina Tschigg²  Gert Flik² 

[1] Animal Sciences and Health Cluster, Institute of Biology, Leiden University, Leiden, Netherlands;Department of Animal Ecology and Physiology, Institute of Water and Wetland Research, Faculty of Science, Radboud University, Nijmegen, Netherlands;

关键词: cortisol;    glucocorticoid receptor;    zebrafish;    larvae;    tail fin regeneration;    lipopolysaccharide;   

DOI  :  10.3389/fimmu.2020.00727

来源: DOAJ

【 摘 要 】

In this study we have assessed the effects of increased cortisol levels during early embryonic development on immune function in zebrafish (Danio rerio) larvae. Fertilized eggs were exposed to either a cortisol-containing, a dexamethasone-containing (to stimulate the glucocorticoid receptor selectively) or a control medium for 6 h post-fertilization (0–6 hpf). First, we measured baseline expression of a number of immune-related genes (socs3a, mpeg1.1, mpeg1.2, and irg1l) 5 days post-fertilization (dpf) in larvae of the AB and TL strain to assess the effectiveness of our exposure procedure and potential strain differences. Cortisol and dexamethasone strongly up-regulated baseline expression of these genes independent of strain. The next series of experiments were therefore carried out in larvae of the AB strain only. We measured neutrophil/macrophage recruitment following tail fin amputation (performed at 3 dpf) and phenotypical changes as well as survival following LPS-induced sepsis (150 μg/ml; 4–5 dpf). Dexamethasone, but not cortisol, exposure at 0–6 hpf enhanced neutrophil recruitment 4 h post tail fin amputation. Cortisol and dexamethasone exposure at 0–6 hpf led to a milder phenotype (e.g., less tail fin damage) and enhanced survival following LPS challenge compared to control exposure. Gene-expression analysis showed accompanying differences in transcript abundance of tlr4bb, cxcr4a, myd88, il1β, and il10. These data show that early-life exposure to cortisol, which may be considered to be a model or proxy of maternal stress, induces an adaptive response to immune challenges, which seems mediated via the glucocorticoid receptor.

【 授权许可】

Unknown