Exosomes act as decoys to protect against bacterial toxins

A recent study published in the journal Nature online March 4 showed that mammalian cells protect them from bacterially produced toxins by a decoy mechanism. This is a newly discovery of exosome's role for cell survival.

When exposed to the bacterial condition, cells are usually killed because bacteria-produced toxins bind to the cell-surface ADAM10 to form holes in the plasma membranes. Previous study has proved that cells derived from mice with hypomorphic expression of ATG16L1 (ATG16L1HM) display an increase in total ADAM10 levels and are prone to lysis during infection. And the autophagy protein ATG16L1 is obligatory to protect cells against bacterial toxins. However, it was unknown whether cells possess innate immune mechanisms that can neutralize pore-forming toxins when they suffer from infection.

Ken Cadwell and his colleagues found that bacteria-exposed cells lived due to the presence of ADAM10-containing exosomes in the cell culture fluid. And they isolated these exosomes from the supernatant and then transferred them into the bacteria-infected mice, improving the survival of mice infected with Staphylococcus aureus (MRSA) in vivo, suggesting that multiple toxins are cleared. A decoy mechanism that prompts cell survival was uncovered, namely, toxins generated by bacteria are trapped to ADAM10-containing exosomes prior to associate with host cell-surface ADAM10. They further identified bacterial DNA and CpG DNA induced the production of exosomes by testing several bacterially derived products. ATG16L1 and other ATG proteins are found to mediate the release of ADAM10-bearing exosomes independently of lysosomal degradation. The process progressed in a manner different from conventional degradative autophagy and appeared to suppress the advanced-stage autophagy to turn to the autophagy machinery towards generation of exosomes.

The researchers thought the decoy mechanism is indeed a defense mechanism for host species to sequester the toxins during infection. It also gains some time for other widely accepted immune defense measures such as bacteria-invading T cells, or antibodies to fight infection directly. In addition to discovering the new mechanism that mammalian defense against infection, their results also provide new and potent strategies for enhancing the immune system, either by injecting artificial, exosome-like vesicles into the body to soak up toxins or by promoting exosome production to consolidate the body's self-defenses.

It is really a good news above that excavates the potential role of exosomes. This further validates the importance of exosomes, much more than what we see now. So it takes more effort to explore more latent valuable roles of exosomes. Since exosomes are usually distributed in a broad spectrum of biological matrices, extracting purified exosomes from these fluids is the premise of any research on exosomes. Therefore, the isolation and purification of exosome is particularly important. How to get exosomes with high-quality and high-yield is a hot topic in the research field. Although there are several traditional exosome separation techniques at present, it is a little difficult to get purified and high-yield exosomes due to the disadvantages of these ways, respectively. With the rising demanding for exosome research, scientific research personnel desire for simple, efficient, and affordable techniques to isolate exosomes. Therefore, some commercial kits that are designed and developed to isolate and purify exosomes have been emerging.

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Story Source:

New York University Langone Health/ New York University School of Medicine. "Newfound cell defense system features toxin-isolating 'sponges'." ScienceDaily. ScienceDaily, 4 March 2020.

Journal Reference:

[1] Matthew D. Keller, Krystal L. Ching, et al. Decoy exosomes provide protection against bacterial toxins [J]. Nature, 2020; 579 (7798): 260.

[2] Maurer, K. et al. Autophagy mediates tolerance to Staphylococcus aureus alpha-toxin [J]. Cell Host Microbe 17, 429–440 (2015).

[3] Inoshima, I. et al. A Staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice [J]. Nat. Med. 17, 1310–1314 (2011).