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Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C

Ingelsson, Björn ; Söderberg, Daniel ; Strid, Tobias LU ; Söderberg, Anita ; Bergh, Ann Charlotte ; Loitto, Vesa ; Lotfi, Kourosh ; Segelmark, Mårten LU ; Spyrou, Giannis and Rosén, Anders (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
; ; ; ; ; ; ; ; and
publishing date
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}},
}