Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C
(2018) In Proceedings of the National Academy of Sciences of the United States of America 115(3). p.478-487- Abstract
Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning... (More)
Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning structure, reactive oxygen species (ROS) dependence, and were devoid of antibacterial proteins. mtDNA webs acted as rapid (within minutes) messengers, priming antiviral type I IFN production. In summary, our findings point at a previously unrecognized role for lymphocytes in antimicrobial defense, utilizing mtDNA webs as signals in synergy with cytokines and natural antibodies, and cast light on the interplay between mitochondria and the immune system.
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- author
- Ingelsson, Björn ; Söderberg, Daniel ; Strid, Tobias LU ; Söderberg, Anita ; Bergh, Ann Charlotte ; Loitto, Vesa ; Lotfi, Kourosh ; Segelmark, Mårten LU ; Spyrou, Giannis and Rosén, Anders
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- keywords
- CpG-C, DAMP, Immune DNA sensing, Lymphocyte signaling, Mitochondrial DNA release
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 115
- issue
- 3
- pages
- 478 - 487
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:85042104216
- pmid:29295921
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.1711950115
- language
- English
- LU publication?
- no
- id
- f8c9769c-7e2c-4f09-ba12-694dcf6cbc13
- date added to LUP
- 2020-06-23 16:41:53
- date last changed
- 2024-06-27 20:40:36
@article{f8c9769c-7e2c-4f09-ba12-694dcf6cbc13, abstract = {{<p>Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning structure, reactive oxygen species (ROS) dependence, and were devoid of antibacterial proteins. mtDNA webs acted as rapid (within minutes) messengers, priming antiviral type I IFN production. In summary, our findings point at a previously unrecognized role for lymphocytes in antimicrobial defense, utilizing mtDNA webs as signals in synergy with cytokines and natural antibodies, and cast light on the interplay between mitochondria and the immune system.</p>}}, author = {{Ingelsson, Björn and Söderberg, Daniel and Strid, Tobias and Söderberg, Anita and Bergh, Ann Charlotte and Loitto, Vesa and Lotfi, Kourosh and Segelmark, Mårten and Spyrou, Giannis and Rosén, Anders}}, issn = {{0027-8424}}, keywords = {{CpG-C; DAMP; Immune DNA sensing; Lymphocyte signaling; Mitochondrial DNA release}}, language = {{eng}}, number = {{3}}, pages = {{478--487}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences of the United States of America}}, title = {{Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C}}, url = {{http://dx.doi.org/10.1073/pnas.1711950115}}, doi = {{10.1073/pnas.1711950115}}, volume = {{115}}, year = {{2018}}, }