Because granulomas are a hallmark of tuberculosis (TB) pathogenesis, the study of the dynamic changes in their cellular composition and morphological character can facilitate our understanding of TB pathogenicity. Adult zebrafish infected with Mycobacterium marinum (M. m) form granulomas that are similar to the granulomas in human TB patients and therefore have been used to study host-mycobacterium interactions. Most studies of zebrafish granulomas, however, have focused on necrotic granulomas, while a systematic description of the different stages of granuloma formation in the zebrafish model is lacking. Here, we characterized the stages of granulomas in M. m infected zebrafish, including early immune cell infiltration, non-necrotizing granulomas and necrotizing granulomas, using corresponding samples from pulmonary TB patients as references. We combined hematoxylin and eosin (H&E) staining and in situ hybridization (ISH) to identify the different immune cell types and follow their spatial distribution in the different stages of granuloma development. The macrophages in zebrafish granulomas were shown to belong to distinct subtypes: epithelioid macrophages, foamy macrophages, and multinucleated giant cells. By defining the developmental stages of zebrafish granulomas and the spatial distribution of the different immune cells they contain, this work provides a reference for future studies of mycobacterial granulomas and their immune microenvironments.
Keyphrases
- mycobacterium tuberculosis
- end stage renal disease
- ejection fraction
- peritoneal dialysis
- prognostic factors
- pulmonary tuberculosis
- endothelial cells
- pulmonary hypertension
- emergency department
- pseudomonas aeruginosa
- induced apoptosis
- cystic fibrosis
- oxidative stress
- cell proliferation
- human immunodeficiency virus
- induced pluripotent stem cells
- electronic health record
- pluripotent stem cells