Abstract
Glucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this study, we have used a larval zebrafish model for tuberculosis, based on Mycobacterium marinum (Mm) infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemic Mm infection. The exacerbated Mm infection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific for Mm, since it was also observed upon infection with Salmonella Typhimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.
Highlights
Glucocorticoids (GCs) are a class of steroid hormones that are secreted upon stress
We found that the bacterial burden increased by 2.3 fold when embryos were treated with 25 mM beclomethasone compared with the vehicle-treated group (Figures 1A, C)
These data suggest that the observed inhibition of phagocytosis upon beclomethasone treatment causes a decrease in the percentage of intracellular bacteria, which underlies the lower numbers of macrophages undergoing cell death as a result of the Mm infection
Summary
Glucocorticoids (GCs) are a class of steroid hormones that are secreted upon stress. The main endogenous GC in our body, cortisol, helps our bodies adapt to stressful situations and for this purpose it regulates a wide variety of systems, like the immune, metabolic, reproductive, cardiovascular and central nervous system. These effects are mediated by an intracellular receptor, the glucocorticoid receptor (GR), which acts as a ligand-activated transcription factor. Synthetic GCs are widely prescribed to treat various immunerelated diseases due to their potent suppressive effects on the immune system. In order to better understand these complex effects of GCs, more research is required into how GCs influence the susceptibility to infections and the course of infectious diseases
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