Mitochondrial DNA in exosomes is the alarm that initiates the antiviral response

July 10, 2018, Centro Nacional de Investigaciones Cardiovasculares
Mitochondrial DNA in exosomes is the alarm that initiates the antiviral response. Credit: CNIC

Researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) 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 research findings, published today in Nature Communications, contribute to the understanding of the cellular processes initiated at early stages and explain how the distinct cell populations of the immune system communicate to mount an effective response against pathogens.

The CNIC researchers have shown that mitochondrial DNA contained in nanovesicles triggers a state of alertness in recipient that activates an antiviral genetic program. These nanovesicles, known as exosomes, are produced by T lymphocytes and taken up by dendritic cells via intercellular contacts.

The against pathogens requires the specific physical interaction between T lymphocytes 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; in contrast, the identity and effects of the signals received by dendritic cells have received relatively little attention. The present study was performed by the group led by Professor Francisco Sánchez-Madrid, principal investigator of the Intercellular Communication laboratory at the CNIC, head of the Immunology Service at the Hospital la Princesa, and Professor of Immunology at the Universidad Autónoma de Madrid. In previous work, the group demonstrated that T cells can transfer exosomes to dendritic cells during the formation of the immune synapse.

In the new study, the research team describe how these nanovesicles "transport DNA and proteins of mitochondrial origin," explained Prof. Sánchez Madrid.

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 DNA present in the nanovescicles is "directly responsable for the increased expression of antiviral genes via the cGAS/STING pathway, resulting in the detection of DNA outside of the cell nucleus." As study author Daniel Torralba explained, "the imported DNA acts as an alarm that triggers the immune system to activate the antiviral response." The study confirms that the acquisition of the exosomal contents induces "this expression of antiviral genes" that protects against viral infection.

This finding opens up a new perspective on the role of extracelular vesicles in the horizontal transfer of mitochondrial components.

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. In the study, authors Daniel Torralba and Francesc Baixauli collaborated with other CNIC groups, including the group led by Professor José Antonio Enriquez and the Proteomics and Genomics units. The study also involved contributions from researchers from the Centro de Investigación CIMA in Pamplona and other Spanish centers.

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 , 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.

Explore further: Boosting cancer therapy with cross-dressed immune cells

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

Related Stories

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

Changes to mitochondrial metabolism allow the immune system to adapt to infection

June 27, 2016
The immune system is equipped with the mechanisms to adapt to bacterial infection, and one of the keys to this efficient reaction is rooted in changes that take place in the metabolism of mitochondria. These changes are important ...

How genetically engineered viruses develop into effective vaccines

July 26, 2017
Lentiviral vectors are virus particles that can be used as a vaccine to stimulate the immune system to fight against specific pathogens. The vectors are derived from HIV, rendered non-pathogenic, and then engineered to carry ...

The STING of death in T cells

September 5, 2017
The cells of the innate immune system use a signaling pathway comprising STING (Stimulator of interferon genes) to detect DNA from invading viruses and fight them. However, it is unknown if STING triggers the same or different ...

Study provides insights on immune cells involved in kidney disease

December 7, 2017
Researchers have uncovered new information on cells involved in the body's immune response following kidney injury. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), ...

Recommended for you

Thymic tuft cells play key role in preventing autoimmunity, mouse experiments show

July 18, 2018
UC San Francisco researchers were recently surprised to discover fully formed gut and skin cells in the thymus, a lemon-sized organ that sits in front of the heart and is responsible for training the T cells of the immune ...

Autism risk determined by health of mom's gut, research reveals

July 18, 2018
The risk of developing autism-spectrum disorders is determined by the mother's microbiome—the collection of microorganisms that naturally live inside us—during pregnancy, new research from the University of Virginia School ...

New findings suggest allergic responses may protect against skin cancer

July 17, 2018
The components of the immune system that trigger allergic reactions may also help protect the skin against cancer, suggest new findings.

The immune system: T cells are built for speed

July 17, 2018
Without T cells, we could not survive. They are a key component of the immune system and have highly sensitive receptors on their surface that can detect pathogens. The exact way that these receptors are distributed over ...

Broadly acting antibodies found in plasma of Ebola survivors

July 17, 2018
Recent Ebola virus disease (EVD) outbreaks, including the 2013-2016 epidemic that ravaged West Africa and the 2018 outbreak in the Democratic Republic of the Congo, highlight the need for licensed treatments for this often-deadly ...

How protein fragments could help to tackle the cause of hay fever

July 16, 2018
Imperial researchers are looking to protein fragments to help people build up resistance to grass pollen.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.