PUBLICATION

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

Authors
Xie, Y., Xie, J., Meijer, A.H., Schaaf, M.J.M.
ID
ZDB-PUB-210529-5
Date
2021
Source
Frontiers in immunology   12: 618569 (Journal)
Registered Authors
Meijer, Annemarie H., Schaaf, Marcel J. M.
Keywords
Mycobacterium marinum, glucocorticoids, macrophage, phagocytosis, tuberculosis, zebrafish
MeSH Terms
  • Animals
  • Bacterial Load
  • Beclomethasone/metabolism
  • Glucocorticoids/adverse effects*
  • Immunophenotyping
  • Immunosuppressive Agents/adverse effects
  • Macrophage Activation/drug effects
  • Macrophage Activation/genetics
  • Macrophage Activation/immunology
  • Macrophages/drug effects*
  • Macrophages/immunology*
  • Macrophages/metabolism
  • Mycobacterium Infections, Nontuberculous/immunology*
  • Mycobacterium Infections, Nontuberculous/metabolism
  • Mycobacterium Infections, Nontuberculous/microbiology*
  • Mycobacterium marinum/drug effects*
  • Mycobacterium marinum/immunology*
  • Phagocytosis/drug effects*
  • Phagocytosis/immunology*
  • Reactive Oxygen Species/metabolism
  • Receptors, Glucocorticoid/metabolism
  • Zebrafish
PubMed
34046029 Full text @ Front Immunol
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.
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