Exosomes play a crucial role in infections as carriers of pathogenic substances. They can directly transmit pathogen-related molecules and also indirectly influence the progress of infection by modulating processes, such as immune evasion and apoptosis. Exosomes can promote further infection by delivering bacterial molecules involved in pathogenesis. For example, exosomes derived from Staphylococcus aureus harbor the pore-forming bacterial molecule α-toxin (40), and it has been observed that exosomes from cells infected with Bacillus anthracis carry the virulence factor of the lethal toxin to sites distal to infection (4).
The work described (41, 4) sheds new light on how exosomes protect host cells by functioning as cellular decoys. The autophagy protein (ATG16L) is necessary for protection against Staphylococcus aureus, which expresses the α-toxin. This pore-forming toxin binds to metalloprotease, a protein 10 (ADAM) containing the domain of disintegrin and metalloproteinase, on the surface of various target cells and tissues. This study confirmed that ATG16L1 and other ATG proteins mediate protection against α-toxin by releasing ADAM10 into exosomes, which act as scavengers that can bind to the toxin and improve host survival (table).
Some components of the ESCRT machinery are secreted into exosomes and can serve as exosome markers, such as Alix and HRS. Interestingly, they also demonstrated that exosomes derived from infected cells affected a very different subset of genes compared to infection by the bacteria itself or the activation of IFN gamma alone, demonstrating that exosomes play a different role in affecting gene regulation, apart from the effects of cytokines or bacterial cells. Unlike normal cell surface expression of HLA DR in melanoma cells, in the presence of the gB protein, HLA DR was transported alternately through the exosomal secretory pathway and released from exosome cells. Although the specific mechanisms for the exosomal enrichment of selected viral and host proteins or RNAs have not yet been clarified, the data demonstrate that viruses can influence host cells by taking over the cellular exosome secretion machinery.
The secretion of ERGIC-53 in the exosome can increase viral infection by taking advantage of the transporter nature inherent in exosomes. Similarly, exosomes released by B cells carry specific antigen-presenting cell molecules, allowing these exosomes to present the antigen to induce T-cell responses and release cytokines IL-5 and IL-13 (100). The increased duration of intestinal exosomes derived from infected cells provides an interesting idea of exosomal delivery directed to tissues relevant to the course of the infection. The disparity that exists in the expected function of exosomes in bacterial and parasitic infections compared to viral infections, as well as variations in exosome subtypes and in the response of host cells to different pathogens are potential escape routes.
As new results accumulate in research on exosomes for various infectious diseases, it will be interesting to see if the burden of exosomes can also meet a similar indicator function in infectious diseases. Deeper studies on the packaging, release and uptake of exosomes are also needed, especially considering the variation in the observable response of host cells to exosomes that arise from different types of infection. Exosomes are found in all body fluids and different methods have been used to isolate exosomes from different biofluids. In addition, the incubation of exosomes and macrophages containing Nef caused a linear increase in exosome uptake by macrophages.
A microfluidic chip is used to evaluate EpCAM-positive circulating exosomes with plasma exosomes. The release of the hepatitis E virus depends on the exosomal route, with secretory exosomes derived from multivesicular bodies. The association of inflammation with disease development and the potential of exosomes to improve or mitigate inflammatory pathways support the idea that exosomes have the potential to alter the course of a disease. Liquid biopsy of exosomes isolated from patients with prostate cancer revealed that exosomes are enriched with genes that are characteristic of prostate cancer, such as the androgen receptor, kallikreins (KLK), the cyclin-dependent kinase inhibitor 1A (CDKN1A), KLK10, JUN and B2M (microglobulin beta2).
