Scientists find the genetic trigger for immune system response
Mitochondria are the “powerhouse of the cell.” We all learn in biology that they have seemingly one function in the body, converting food and oxygen into energy. Well that might not be the case anymore; the thousands of mitochondrial DNA (mtDNA) molecules present in each cell have been identified in an unexpected relationship with the innate immune response.
The team made this discovery while examining mouse models of mtDNA “stress,” or damage that normally happens during disease and aging. The specific mouse model examined was engineered to lack a gene that supports normal mtDNA stability. What the researchers observed was an antiviral response.
“We were surprised that there was an interferon response, which you would see if you were being infected by a pathogen,” said Gerald Shadel, professor of pathology and genetics at Yale School of Medicine.
“We had cells that looked like they were infected with a virus but they were not.”
This unexpected antiviral activity, without the presence of a virus, may point to new areas of research on human diseases.
“It’s pretty well accepted that mitochondria are involved in inflammatory pathology like that seen in autoimmune diseases,” said Shadel.
The study, however, suggests a new source of inflammation that could promote common diseases and aging. The researchers also tested the effect of certain viruses, such as the herpes simplex virus (HSV), on mtDNA and the antiviral response. They discovered that HSV actually attacked mtDNA during infection, making mtDNA stress or instability a normal, and necessary, part of the way that a cell senses and responds to infection.
“We found a pathway that is leading to an antiviral, pro-inflammatory state. We want to know if the mtDNA instability triggers these pathways, contributing to disease and age-related pathology,”Shadel explained.
This is important since it gives us another pathway to analyze in the understanding of autoimmune diseases, as well as the more mainstream aging and cancer research. However, the first area to which they plan to apply this new knowledge is cancer.
West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, & Shadel GS (2015). Mitochondrial DNA stress primes the antiviral innate immune response. Nature PMID: 25642965