Mycobacterium marinum Infection in Zebrafish and Microglia Imitates the Early Stage of Tuberculous Meningitis

AbstractMycobacterium tuberculosis (M.tuberculosis) invading and activating microglia causes the most serious subtypes of tuberculosis called tubercular meningitis. However, the developmental process of tubercular meningitis, especially the early phase, is poorly understood due to lacking well-established and well-accepted visible models in vitro and in vivo. Here, consistent with one recent report, we foundMycobacterium marinum (M. marinum) invade the zebrafish brain and subsequently cause granuloma-like structures. We further showed thatM.marinum, which shares similar characteristics withM.tuberculosis, can invade microglia and replicate in microglia, which subsequently promote the secretion of pro-inflammatory cytokines such as IL-1 β, IL-6, and TNF-α.M.marinum infection in microglia can also promote autophagy, which conversely limits the replication ofM.marinum. Thus, pharmacological activation of autophagy by rapamycin could preventM.marinum replication. Our study provides in vivo and in vitro models to study underlying pathogenic mechanisms of tubercular meningitis by usingM.marinum. Our results also showed that activation of autophagy could be a meaningful way to prevent tubercular meningitis.

Source: Journal of Molecular Neuroscience - January 20, 2018 Category: Neuroscience Source Type: research