Mycobacteria release active membrane vesicles that modulate immune responses in a TLR2-dependent manner in mice

Rafael Prados-Rosales, et al. J Clin Invest. 2011; 121(4):1471–1483.

Speaker: Kuan-Chih Wu (武冠志)                                Time: 13:10-14:00 Nov. 9, 2011

Commentator: Pei-Jane Tsai Ph.D. (蔡佩珍老師)        Place: Room 601

Abstract:

The membrane vesicles (MVs) are released by many organisms, including animals, fungi and bacteria and are usually used to transport materials from one cell to another. But in some intracellular pathogens, such as mycobacteria, they become a tool to fight against the host immune response by releasing the immunomodulating molecules when the pathogen interacts with host during infection. In a previous study, Mycobacterium ulcerans was shown to produce MVs. In this study, the authors further investigated whether the clinically important mycobacteria, M. tuberculosis and M.bovis bacille Calmette-Guérin, and other mycobacterial species could produce MVs. They also tried to identify the compositions of MVs and understand how MVs modulate host immune response, especially in the TLR2 manner. It was shown that all of the mycobacteria they tested produced MVs, with sizes ranging is between 60nm to 300 nm. The result of isotope metabolic labeling test demonstrated that the MVs of these mycobacteria are produced by living bacteria, but not the dead ones. The authors also analyzed the protein and lipid compositions of MVs of different mycobacteria and found that some components, which have been reported as TLR2 ligands, were enriched in the MVs. The authors further tested whether the MVs modulate host immune response in a TLR2-dependent manner in a TLR2-deficient mouse model, and the data showed that MVs modulate host immune response partly via TLR2. In summary, mycobacterial species produce MVs, which are rich in some components that act asTLR2 ligands to modulate the host immune response as a strategy for some clinically significant mycobacteria to escape from the immune attack.

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