Extracellular Vesicles: Recent Insights Into the Interaction Between Host and Pathogenic Bacteria

Abstract

Extracellular vesicles (EVs) are nanosized lipid particles released by virtually every living cell. EVs carry bioactive molecules, shuttle from cells to cells and transduce signals, regulating cell growth and metabolism. Pathogenic bacteria can cause serious infections via a wide range of strategies, and host immune systems also develop extremely complex adaptations to counteract bacterial infections. As notable carriers, EVs take part in the interaction between the host and bacteria in several approaches. For host cells, several strategies have been developed to resist bacteria via EVs, including expelling damaged membranes and bacteria, neutralizing toxins, triggering innate immune responses and provoking adaptive immune responses in nearly the whole body. For bacteria, EVs function as vehicles to deliver toxins and contribute to immune escape. Due to their crucial functions, EVs have great application potential in vaccines, diagnosis and treatments. In the present review, we highlight the most recent advances, application potential and remaining challenges in understanding EVs in the interaction between the host and bacteria.

Keywords: bacteria; extracellular vesicle (EV); host; host-bacteria interaction; immune response.

Figure 1

Mechanisms of hEVs in the interaction between the host and bacteria. (A) Pore-forming agents lead to Ca2+ influx and activate TMEM16F. Subsequently, damaged membranes are repaired by releasing hEVs. (B) A pH change leads to Ca2+ efflux, and this efflux triggers hEVs release to expel bacteria. (C) Host cells release ADAM10-containing hEVs to neutralize toxins. (D) Cells release molecules such as cytokines via hEVs for innate immunity. (E) Cells present antigens via hEVs for adaptive immunity. (F) Lethal factors of anthrax store in late endosomes sheltering from degradation and are released to the cytosol and the extracellular environment. (G) Bacterial DNA of Listeria monocytogenes is encapsulated into hEVs, and these hEVs stimulate the cGAS-STING pathway of T cells, which primes T cells for apoptosis. This figure was created with BioRender.com.

Figure 2

Potential applications of EVs in interactions between the host and bacteria. EVs have potential in diagnosis, anti-infection therapy, vaccines and antitumor therapy. Combined with specific molecules and other techniques, hEVs may be utilized for fast diagnosis and differential diagnosis. HEVs from specific cells, such as mesenchymal stem cells, possess antibacterial effects, and hEVs combined with other materials may show better therapeutic effects. BEVs contain many pathogen-associated molecular patterns that provoke innate and adaptive immune responses and are suitable for adjuvants and vaccines. Engineered bEVs express specific proteins that demonstrate antitumor effects. Meanwhile, these bEVs are able to load antitumor drugs, showing potential in antitumor therapy. This figure was created with BioRender.com.