Glucocorticoid-Induced Exacerbation of Mycobacterial Infection Is Associated With a Reduced Phagocytic Capacity of Macrophages

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.

Alpha-1-antitrypsin binds to the glucocorticoid receptor with biological significance in macrophages

“…The consensus among clinicians and scientists is that GCs increase susceptibility to Mycobacterium tuberculosis (Jick et al , 2006; Lai et al , 2015) and possibly non-tuberculous mycobacteria (NTM) (Xie et al , 2021). On the other hand, AAT enhances autophagy, an effector mechanism known to kill intracellular mycobacteria (Bai et al , 2019; Bai et al , 2013; Deretic et al , 2006; Gutierrez et al , 2004).…”

Intestinal tuberculosis in a patient with Cushing’s syndrome

“…According to research at Leiden University Netherlands by Xie et al involving larval zebrafish models for tuberculosis to study the effect of glucocorticoids, they have concluded that steroids inhibit the macrophages` phagocytic activity, thereby increasing severity of bacterial infections such as tuberculosis [13] .…”

Reduced phagocytic activity of human alveolar macrophages infected with Mycobacterium avium complex

“…The effects of these agents on the proportion of macrophage phenotypes in the lungs and their phagocytic ability for each phenotype have not yet been clarified. Glucocorticoids have been reported to increase or decrease the phagocytic ability of macrophages [37][38][39]. Further studies are needed to determine the effect of steroids, immunosuppressants, and biologics on the proportion of non-polarized alveolar macrophages and the phagocytic ability of all types of macrophages.…”