Exosomes and membrane vesicles in mycobacterial infection - potential therapeutic applications

Abstract

The purpose of this thesis is to discuss the role of eukaryotic and prokaryotic extracellular vesicles in Mycobacterium tuberculosis infection and their possibilities in future vaccine development. Tuberculosis is global threat of health. Approximately 10 million new tuberculosis cases are diagnosed and almost 1,5 million tuberculosis related deaths are reported annually. Currently there is only one licensed tuberculosis vaccine available, but its efficacy wanes dramatically after childhood. Thus, we are in urgent need of new vaccine. Research during last decade has revealed that extracellular vesicles participate in large amount of cellular processes. In mycobacterial infection, host’s exosomes have a role in generation of immune protection. According to studies host exosomes may include mycobacterial derived molecules. Exosomes may activate both innate and acquired immune systems by activating T cells and enhancing chemokine and cytokine production. It seems that also mycobacterial membrane vesicles have crucial role during infection, especially in promoting it. For example, mycobacterial lipoproteins in bacterial membrane vesicles may affect to toll-like receptors, and thus promote bacterial virulence. Since those vesicles have effect on immune protection and bacterial virulence, by utilizing them it might be possible to create effective vaccine response. During tuberculosis vaccine development several characteristics should be considered. Firstly, Mycobacterium tuberculosis is an intracellular pathogen, which destruction might require cellular responses. Secondly, different stages of tuberculosis infection vary greatly and hence for example its antigen composition changes. Extracellular vesicles have natural features which makes them suitable candidates for vaccine applications. Vesicles cannot divide and thus they lack the capability of causing an infection unlike attenuated bacteria. For this reason, vesicle-based vaccine could be safer than the current vaccine. This might enable its use also with immunocompromised people. Extracellular vesicles have also an ability to work as natural adjuvants, by which they can promote immune protection. Furthermore, both host cell exosomes and bacterial membrane vesicles have suitable physiochemical features enabling them to reach lymph nodes effectively where they can interact with antigen presenting cells. All in all, exosomes and mycobacterial membrane vesicles seems to be potential components of new tuberculosis vaccine. However, extracellular vesicle research is just at the beginning and more research is required.