Researchers Reveal Mitochondrial DNA in Exosomes Triggers Antiviral Response

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Researches from Centro Nacional de Investigaciones Cardiovasculares (CNIC), demonstrated exosomes transferred from T lymphocytes to dendritic cells contain mitochondrial DNA that communicate to mount an effective response to pathogens.

Researchers from CNIC highlighted valuable information on defense mechanisms of the immune system during the early stages of pathogens attack. It was observed that mitochondrial DNA contained in exosomes alarms the recipient cells to activate an antiviral genetic program. These exosomes are produced by T lymphocytes and taken up by dendritic cells via intercellular contacts. The research was published in Nature Communications on July 09, 2018.

An immune response against pathogens requires interaction between T lymphocytes and antigen presenting cells. The cells in this process exchange information both through receptor-ligand contacts at the cell surface and through the transfer of exosomes. Although it is already established that immune synapse activates signaling routes in the T cell, it is unclear about the identity and effects of the signals received by dendritic cells. The present research was led by Professor Francisco Sánchez-Madrid, principal investigator of the Intercellular Communication laboratory at the CNIC. His team previously demonstrated that T cells transfer exosomes to dendritic cells during the formation of the immune synapse. Now, it was observed that mitochondrial components are directed to the endosomal system in the T cell, where the exosomes are formed and later secreted. Both the processes establish a tight relationship between the endosomal and mitochondrial compartments. The DNA present in the exosomes increases the expression of antiviral genes via the cGAS/STING pathway. It enables detection of DNA outside of the cell nucleus, which in turn acts as an alarm that triggers the immune system to activate the antiviral response. Animal models allowed the transfer of mitochondrial DNA to be tracked during the formation of the immune synapse. It showed functional impact on the recipient cells. Exposure to exosomes of T-cell origin alarms alterations in the expression of around 1600 genes in dendritic cells. Such modifications are involved in protection against viral infection.

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