Mycobacteria employ two different mechanisms to cross the blood-brain barrier

Cellular Microbiology
Lisanne M van LeeuwenWilbert Bitter

Abstract

Central nervous system (CNS) infection by Mycobacterium tuberculosis is one of the most devastating complications of tuberculosis, in particular in early childhood. In order to induce CNS infection, M. tuberculosis needs to cross specialised barriers protecting the brain. How M. tuberculosis crosses the blood-brain barrier (BBB) and enters the CNS is not well understood. Here, we use transparent zebrafish larvae and the closely related pathogen Mycobacterium marinum to answer this question. We show that in the early stages of development, mycobacteria rapidly infect brain tissue, either as free mycobacteria or within circulating macrophages. After the formation of a functionally intact BBB, the infiltration of brain tissue by infected macrophages is delayed, but not blocked, suggesting that crossing the BBB via phagocytic cells is one of the mechanisms used by mycobacteria to invade the CNS. Interestingly, depletion of phagocytic cells did not prevent M. marinum from infecting the brain tissue, indicating that free mycobacteria can independently cause brain infection. Detailed analysis showed that mycobacteria are able to cause vasculitis by extracellular outgrowth in the smaller blood vessels and by infecting endothelial cells...Continue Reading

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Oct 26, 2018·Expert Review of Anti-infective Therapy·Ravindra Kumar GargNeeraj Kumar
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Aug 21, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Deodutta RoySeyed Ehtesham Hasnain

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Methods Mentioned

BETA
electron microscopy
confocal
Electron
FACS
Infection
PCR
confocal microscopy

Software Mentioned

BD CFlow
Adobe Photoshop
ImageJ
Leica Application Suite X
CLEM

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