Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C, 2018, Rosen et al

Andy

Andy

Retired committee member
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 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.
Click to expand...
Paywalled at http://www.pnas.org/content/115/3/E478
 
I found a B cell and leukaemia link for myself as the genetic locations mentioned on Ulf Klein (Leeds) Page are likely my genetic locations Axenfeld rieger syndrome that contains autism and mecfs
Research Mention of non Hodgkin lymphoma as well
FOXC1/FOXO1A
Zinc/G protein receptor 39 mentioned as well
 
Last edited:
Last edited:
Hi @janice, thank you for the link. It's useful if you also give the title, date and author, and you can copy an abstract, but not a whole paper.

Your first two links gave me error messages, the third linked to this. I've broken it up for ease of reading:

Mini Review by Song Liu et al.

Mitochondrial DNA sensing by STING signaling participates in inflammation, cancer and beyond

Abstract

Recent studies have revealed the diverse pathophysiological functions of mitochondria beyond traditional energetic metabolism in cells.

Mitochondria-released damage-associated molecular patterns, particularly mitochondrial deoxyribonucleic acid (mtDNA), play a central role in host immune defenses against foreign pathogens.

Newly discovered cGAS-STING signaling is responsible for microbial DNA recognition, and potentially participates in mitochondrial DNA sensing.

Inappropriate inflammatory signaling mediated by mtDNA is implicated in various human diseases, especially infectious/inflammatory disease and cancer.

In addition, mtDNA horizontal transfer between tumor cells and surrounding somatic cells has been recently observed and been associated with tumorigenesis and cancer progression.

In this review, we will summarize the molecular signaling of mtDNA recognition (especially STING signaling), and discuss the underlying mechanism by which mtDNA transfer triggers cancer progression in human.

Besides, we will highlight the central role of mtDNA in host immunity, with particular emphasis on mtDNA-induced NETs (neutrophil extracellular traps) formation, apoptosis and autophagy.

http://onlinelibrary.wiley.com/doi/...riods+of+downtime+or+disruption+in+the+future.
 
I found this a useful review to get to know the background of recent Immunological advances.

It has the advantage of being in a high impact paper and again has lots of useful refs.

Plus mentions of T and B cell homeostasis, PAMPS, DAMPS, etc which I found very helpful to get context.

J Immunol. 2012 July 1; 189(1): 15–20. doi:10.4049/jimmunol.1102108.

"Autophagy – an emerging immunological paradigm"

Author : Vojo Deretic* of Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences
Center, 915 Camino de Salud, NE, Albuquerque, NM 87131 USA

Abstract
Autophagy is a fundamental eukaryotic process with multiple cytoplasmic homeostatic roles, recently expanded to include unique standalone immunological functions and interactions with nearly all parts of the immune system.

Here, we review this growing repertoire of autophagy roles in innate and adaptive immunity and inflammation.

Its unique functions include cell-autonomous elimination of intracellular microbes facilitated by specific receptors.

Other intersections of autophagy with immune processes encompass effects on inflammasome activation and secretion of its substrates including IL-1β, effector and regulatory interactions with Toll-like and Nod-like receptors, antigen presentation, naïve T cell repertoire selection, and mature T cell development and homeostasis.

Genome wide association studies in human populations strongly implicate autophagy in chronic inflammatory disease and autoimmune disorders.

Collectively, the unique features of autophagy as an immunological process and its contributions to other arms of the immune system represent a new immunological paradigm.

I know it's a bit old 2012 and so many has been used before?

Anyway I hope it helps?
 
You must log in or register to reply here.
Back
Top Bottom