Like billions of supporting military units in addition to immune cells in the body, eukaryotic cells contained in all mammals also add to the body’s immune system via their own cellular self-defense. Eukaryotic cells are composed of compartments separated by selectively permeable barriers which control their composition, each representing their own microenvironment with the potential to harm invading microorganisms. These barriers physically prevent pathogens from gaining entry, with integrated sensors that are activated by foreign bodies. When pathogens do gain access to these cellular compartments, the resulting damage to the host cell body allows the release of potent antimicrobial effectors. However, even though this system is highly effective, it is still unclear why superbugs such as MRSA infect some people whilst others are able to fight these bacteria off. Now, a study from researchers at NYU Grossman School of Medicine identifies a previously unknown cell-based defense in mammals. The team states human and animal cells exposed to the MRSA bacteria release tiny, protein-coated packages called exosomes, which act like sponges to soak up and neutralize bacterial toxins. The study is published in the journal Nature.
Past studies from the group investigating immune responses showed cells lived longer or survived a bacterial infection contained a protein called ATG16L1 in their compartments, with cells lacking ATG16L1 dying. ATG16L1 is a protein involved in autophagy, the destruction and recycling of damaged or redundant cellular components. It was noted previously by the group the action of extracellular exosomes mirrors the ATG16L1-mediated autophagy pathway observed in their experiments. The current study investigates whether ATG16L1, along with other ATG proteins, are involved in the release of extracellular exosomes during a bacterial attack outside the cell wall.
The current study injects mice with the MRSA superbug and heightens their immunity using exosomes extracted from mice infected by the same bacterium previously. Results show twice as many mice survived and lived longer than the mice infected with MRSA did not receive the immune-boosting exosome injection. In vitro experiments were also used to show both human and mice cells die when exosome production is chemically or genetically blocked, indicating the crucial role these vesicles play in cellular survival. Data findings show bacterium DNA and part of the cell’s own DNA triggers the production of exosomes carrying ADAM10, whose primary function is to stick to the pathogen, split its outer membrane and disintegrate its contents.
Results show ATG proteins regulate a previously unknown form of defense in response to infection, facilitating the release of exosomes serving as decoys for bacterially produced toxins. The lab states their data indicates exosomes protect host cells in vitro by serving as scavengers with the ability to bind multiple toxins, and improve the survival of mice infected with MRSA in vivo. They go on to add this newly discovered cell defense system explains why one-fifth of Americans have MRSA bacteria on their body yet only 1 in 10,000, die from an infection.
The team surmises they have discovered a previously unknown mammalian cell defense that soaks up toxins like a sponge. For the future, the researchers state they provide new strategies for increasing immunity, either by injecting synthetic exosomes into the body to soak up toxins or by raising exosome production to fortify the body’s defenses.
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