A study explores the role of mitochondrial DNA webs in immune response. When damaged cells release pathogen-associated and danger-associated molecular patterns, cellular receptors activate signaling cascades in the innate immune system. Recent studies have focused on circulating mitochondrial DNA (mtDNA) as a potent danger-associated molecular pattern (DAMP) molecule, which is associated with trauma, autoimmune disorders, and certain cancers. Anders Rosen and colleagues report that human lymphocytes--B cells, T cells, and natural killer cells--as well as monocytes and neutrophils respond to the presence of CpG and non-CpG oligodeoxynucleotides of class C by releasing extracellular mtDNA web structures that rapidly signal the presence of a threat. Using immune cells derived from both healthy blood donors and patients with lymphocytic leukemia, the authors found that the webs differ structurally from neutrophil extracellular traps, a well-established immune response to bacterial challenges. Once ejected, the webs rapidly initiate the production of antiviral type I interferon (IFN). The findings suggest that lymphocytes have a previously unreported role in innate immune system signaling in which mtDNA act as a rapid antimicrobial messenger molecule. In addition, lymphocyte-derived mtDNA DAMPs may play a role in inflammatory diseases and cancers linked to excessive type I IFN production, according to the authors.
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Article #17-11950: "Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C," by Björn Ingelsson et al.
MEDIA CONTACT: Anders Rosén, Linköping University, Linköping, SWEDEN; e-mail: < Anders.Rosen@liu.se >
Proceedings of the National Academy of Sciences