Mitochondrial DNA in Exosomes is the Alarm That Initiates the Antiviral Response

Source: Centro Nacional de Investigaciones Cardiovasculares

Summary: Researchers have provided valuable information about the defense mechanisms of the immune system during the early stages of the response to pathogens such as viruses and bacteria.

The immune response against pathogens requires the specific physical interaction between Tlymphocytes and antigen-presenting cells, especially dendritic cells, through the formation of an immune synapse. During this process, the cells exchange information both through receptor-ligand contacts at the cell surface and through the transfer of exosomes. Research to date has focused on how the immune synapse activates signaling routes in the T cell. Researchers from the CNIC have shown that mitochondrial DNA contained in nanovesicles triggers a state of alertness in recipient cells that activates an antiviral genetic program. These nanovesicles, known as exosomes, are produced by T lymphocytes and taken up by dendritic cells via inter-cellular contacts. The study findings were published in the journal Nature Communications.

DNA located in mitochondria

Mitochondrial DNA in exosomes is the alarm that initiates the antiviral response. Credit: CNIC

In the new study, the research team describes how these nanovesicles “transport DNA and proteins of mitochondrial origin. The study reveals that the mitochondrial components are directed to the endosomal system in the T cell, where the exosomes are formed and later secreted, demonstrating the tight relationship between the endosomal and mitochondrial compartments. The research team used animal models with distinct mitochondrial DNA genotypes, thus allowing the transfer of mitochondrial DNA to be tracked during the formation of the immune synapse. The transfer of DNA in exosomes has a functional impact on the recipient cells. Exposure to exosomes of T-cell origin triggers alterations in the expression of around 1600 genes in dendritic cells, and many of these modified genes are involved in the protection against viral infection.

These discoveries contribute to the understanding of the cellular processes initiated during the immune synapse and of how components of the innate and adaptive immune systems communicate to mount an effective response to pathogens.

More Information: Daniel Torralba et al, “Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts”, Nature Communications (2018). DOI: 10.1038/s41467-018-05077-9 

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