Research Papers: Immunology:

Lack of intracellular replication of M. tuberculosis and M. bovis BCG caused by delivering bacilli to lysosomes in murine brain microvascular endothelial cells

Xi Chen, Kaori Sakamoto, Frederick D. Quinn, Huanchun Chen and Zhenfang Fu _

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Oncotarget. 2015; 6:32456-32467. https://doi.org/10.18632/oncotarget.5932

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Xi Chen1,2, Kaori Sakamoto2, Frederick D. Quinn3, Huanchun Chen1 and Zhenfang Fu1,2

1 State-key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China

2 Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA

3 Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA

Correspondence to:

Kaori Sakamoto, email:

Zhenfang Fu, email:

Keywords: mycobacterium; endothelial cells; cytotoxicity; trafficking; cell-to-cell spread; Immunology and Microbiology Section; Immune response; Immunity

Received: June 28, 2015 Accepted: September 14, 2015 Published: September 30, 2015


Invasion and traversal of the blood-brain barrier (BBB) by Mycobacterium tuberculosis cause meningeal tuberculosis (TB) in the central nervous system (CNS). Meningeal TB is a serious, often fatal disease that disproportionately affects young children. The mechanisms involved in CNS invasion by M. tuberculosis bacilli are poorly understood. In this study, we microscopically examined endosomal trafficking and measured survival of M. tuberculosis and M. bovis Bacille Calmette-Guérin (BCG) bacilli in murine brain microvascular endothelial cells (BMECs). The results show that both species internalize but do not replicate in BMECs in the absence of a cytotoxic response. Confocal microscopy indicates that bacilli-containing vacuoles are associated with the early endosomal marker, Rab5, late endosomal marker, Rab7, and lysosomal marker, LAMP2, suggesting that bacilli-containing endosomes mature into endolysosomes in BMECs. Our data also show that a subset of intracellular M. tuberculosis, but not BCG bacilli, escape into the cytoplasm to avoid rapid lysosomal killing. However, the intracellular mycobacteria examined cannot spread cell-to-cell in BMECs. Taken together, these data show that with the exception of the small terminal cytoplasmic population of bacilli, M. tuberculosis does not modulate intracellular trafficking in BMECs as occurs in macrophages and lung epithelial and endothelial cells.

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