Category Archives: Inflammatory and Immune System

Rheumatoid arthritis, connective tissue diseases, autoimmune diseases, allergies and normal development and function of the immune system

What the immune system is up to while you’re holding your breath

Ingrid EftedalBlogger: Ingrid Eftedal, Principal investigator
Barophysiology research group, Department of circulation and medical imaging

 

 

White blood cells are essential components of the immune system. Without these cells we would not stay healthy for long on a planet where infections thrive. But what are these cells up to when we’re not sick? They are present. And they are active, at all times.

Lean back and breathe in. Hold your breath. It can’t get much easier; what could there possibly here for a scientist to study? Well, there is something.

Evolution has shaped us for the environment we live in, and our environment is never completely static. The immune system is involved in rapid biological adjustments that protect us from harm caused by environmental perturbations. Some perturbations are of a cyclic nature, like those that are linked to the earth’s rotation around the sun and its own axis. In an elegant study published in the journal Nature in 2015, English and German scientists identified variations in the immune system that are perfectly aligned with the seasons. Actually, our bodies appear to lie slightly ahead of the seasonal changes: we appear to have a biological memory that fine-tunes the immune system just before the seasons change. Since many common infectious diseases appear in a seasonal pattern, this is an amazing adaptation for life on planet earth. If we speed the cycle up a bit, related effects have been observed over the 24 hrs cycle.

So the immune system shows cyclic variation.

What happens if we speed it up to the cycle of our breath?

Most of the time, we breathe without thinking about it. Our cells need oxygen for energy production, and once we have filled our lungs with air, it is the circulatory system – i.e. the heart, blood vessels and blood – that distributes oxygen to the cells in all parts of our body. We can all voluntarily hold our breath for a while, but some people do this better than the rest. Freedivers dive while holding their breath; the best of them can hold their breath for over 10 minutes.

Freediving competition.

Eleven-time free-diving world champion Goran Colak during a bout of static apnea; timed breath-holding while immersed in water .We have used blood samples from elite free-diving athletes to examine how white blood cells of the immune system responds to acute reduction in blood oxygen levels. The photo is used with Goran Colak’s permission.

In order to understand how white blood cells respond to an altered breathing pattern, we studied some of the world’s best free-diving athletes. We used a simple design: blood samples were drawn from contestants at an international free-diving competition before start, and then again one and three hours after completion of a series of dives where the athletes either lay face down in water or swam close to the surface for as long as they could.

Then the samples were transported to the NTNU Genomic Core Facility where total gene expression in the athletes’ white blood cells was measured by a method called full genome microarray analysis. The analysis results were striking: the activity of more than 5000 genes changed in response to the simple effort of breath-holding. This is almost ¼ of all genes found in human cells. With this amount of data we could dig deeper into cellular biology and calculate which specific types of white blood cells that reacted to breath-holding, and also see finer details in the biological processes going on within the cells.

Graph showing white blood cell types in freedivers.

The figure shows a selection of white blood cell types in samples taken from athlete free-divers. Blue boxes are cell amounts prior to diving, whereas the red and green boxes show the same cells one and three hours after diving. The main changes identified were a marked increase in the amount of neutrophil granulocytes, whereas two types of lymphocytes; CD8-postivie cells and natural killer (NK) cells, decreased. Calculations of relative amounts of specific white blood cell types were done by mathematical deconvolution of global blood gene expression data.

The most striking finding we did was a marked increase of the white blood cell type neutrophil granulocytes. These blood cells are programmed for rapid response when the body perceives attacks from intruders; the neutrophils are capable of killing invading cells simply by eating them. But they also have another interesting trait that emerges when oxygen levels drop: neutrophil granulocytes are evolutionary old-timers that stem from an era when the atmosphere contained less oxygen than now, and their modern offspring still prefer environments where the oxygen levels are low. White blood cell types that use more oxygen – like lymphocytes – were less active in blood drawn after the athletes held their breath. What we observed are likely to be traces of evolutionary history still embedded in our immune system, visible when oxygen levels change. The study was published in November 2016 in the journal Physiological Genomics.

This study was done on healthy athletes.

Can it be relevant for understanding of human diseases?

Healthy people normally don’t have to worry about oxygen, but for common diseases like chronic obstructive lung disease (COPD) and sleep apnea, the body’s oxygen supply is limited. These diseases are associated with persistent inflammatory conditions, and increased risk of infections; both indicative of an impaired immune system. If we can use data from healthy individuals to distinguish secondary effects of low oxygen levels from the primary pathology of the disease, this may in turn be helpful for prevention and treatment strategies.

– And breathe out.

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CEMIR received Young Research Talents grant (FRIPRO) from the Research Council of Norway

Two researchers at CEMIR, Atle Granlund and Richard Kandasamy have received the “Young Research Talents” – grants that is a part of the FRIPRO-funding (Norwegian link) for researchers early in their career.  FRIPRO is an open, national competitive arena that covers all fields of research. It aims to promote scientific quality at the forefront of international research, boldness in scientific thinking and innovation, careers for young research talents and mobility for researchers early in their career. FRIPRO aims to contribute to strengthen Norway’s national knowledge base by funding broad-based, independent research, that is a prerequisite for all other research and is essential for future industrial development and for policymaking. Continue reading

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Tuberculosis – a complex enigma

Blogger: Jane Atesoh Awuh, Postdoctoral Fellow, Department of Cancer Research and Molecular Medicine and Centre of Molecular Inflammation Research (SFF-CEMIR).20161125_133429 crop

Most often we become passionate and involved in issues in this life for very personal reasons. I am particularly drawn to infectious diseases because I hail from a society that is plagued by one kind of infection or the other. If you are not killed by one infectious disease you will be by the other, and if not by disease, it will be by war or hunger. I know two relatives who died of tuberculosis, one of them only a couple of months ago. Tuberculosis (TB) is still a disease of poverty although there is increasing incidence even in developed countries. HIV and TB are a dangerous liaison wherein HIV infects and destroys the very cells that should protect us from TB. These diseases are still considered shameful and surrounded by stigma. Continue reading

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Mapping the antiviral innate immune defense system

Trondheim 03.06.2016: Richard Kumaran Kandasamy, Onsager Fellow and Associate Professor, Centre of Molecular Inflammation Research (SFF-CEMIR), Norwegian University of Science and Technology. Photo: Thor Nielsen.

Blogger: Richard Kumaran Kandasamy Associate Professor and Onsager Fellow at Centre of Molecular Inflammation Research (SFF-CEMIR)

Our innate immune system is the first and most important barrier of microbial threats such as viruses and bacteria.  It will sense, and in most cases, clear out these pathogens – but not always. A new approach to studying macrophage response to viral threats have resulted in a vastly expanded knowledgebase of the dynamics of the host response to viral infection, and in turn how antiviral innate immunity works. The data is freely available at www.infectome-map.org. Continue reading

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New insight in the development of immunity to parasitic worms

Menno-Oudhoff-Foto-Jacob-jensen-BloggBy Menno Oudhoff,
Researcher, Centre of Molecular Inflammation Reseach (CEMIR)

 

 

The gastrointestinal tract is a common site for infection by a variety of pathogens. Helminth infections continue to be major causes of disease worldwide, and are a significant burden on health care systems. For example, gut-dwelling parasitic worms currently infect over a billion people, mostly in developing nations. Deworming strategies have been shown to improve physical and intellectual development of infected children, but current therapies do not offer a sustainable solution.

Trichuris worms

Intestinal tissue infected by Trichuris worms

We still have too little insight into how these pathogens are causing disease and how immunity to them is regulated.

Group leader at Centre of Molecular Inflammation research (CEMIR) Menno Oudhoff, together with scientists in Vancouver and Melbourne, have published results from a recent study in PLOS Pathogens. Their study shows that SETD7, an enzyme that modifies the function of other proteins by methylation, plays an important role in the development of intestinal immunity to the helminth parasite Trichuris muris. Specifically, they show that SETD7 affects intestinal epithelial turnover, a key mechanism through which T. muris worms are extruded from the body.

The studies identify pathways that are important for immunity to infection, that were previously believed to be involved primarily during embryonic development.

Research article:

Intestinal Epithelial Cell-Intrinsic Deletion of Setd7 Identifies Role for Developmental Pathways in Immunity to Helminth Infection

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Successful international conference on molecular inflammation in Trondheim

May 30th – June 2nd CEMIR organized an international conference on mechanisms of molecular inflammation. The venue was Kunnskapssenteret at NTNU/ St. Olavs Hospital.

 CEMIR director Terje Espevik opened the conference


CEMIR director Terje Espevik opened the conference. Photo: Ann-Charlotte Iversen

200 delegates from 20 different countries participated and made this conference an important arena to foster further innovative research on molecular mechanisms and regulation of inflammation. The conference brought together scientists from basic and clinical research and provided significant insight into common underlying processes of inflammatory disorders that can be translated to clinical settings. Continue reading

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Richard Kandasamy receives Onsager Fellowship

RKandadsamiAssociate Professor Richard Kumaran Kandasamy at the Centre of Molecular Inflammation Research has received an Onsager Fellowship at NTNU. The Onsager Fellowship Programme is designed to recruit young, internationally recognized researchers to strengthen the university’s academic community.

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CEMIR Annual Report 2015

CEMIR_AnnualReport_2015_LAST-VERSION-1CEMIR has released its 2015 Annual Report. The scientific activities at CEMIR have proceeded with very good progress. In 2015, 77 papers have been published. CEMIR researchers have published a total of 144 articles since 2013, several in high quality journals like Journal of Immunology, Nature, Nature Immunology, Autophagy and PNAS. Eight PhD Candidates completed their theses at the centre in 2015.

Read more about these results and more scientific highlights in the annual report:
CEMIR Annual Report 2015 (pdf)

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Unveiling connections between preeclampsia and cardiovascular disease

Women with preeclampsia have up to eight times higher risk of later developing cardiovascular disease. CEMIR’s research group on Inflammation and Genetics in Pregnancy studies how the development of preeclampsia and cardiovascular disease are connected.

ISSHP

Liv Cecilie Vestrheim Thomsen (left) and Lobke Gierman.

The group has recently unveiled inflammatory mechanisms in the placenta and identified an important role for fetal trophoblasts. They have also identified a gene variant that is protective for both preeclampsia and cardiovascular disease.

This research was recently presented at the International Society for the Study of Hypertension in Pregnancy (ISSHP), a conference about research and treatment of hypersensitive diseases during pregnancy, primarily preeclampsia and gestational hypertension.

Researcher Liv Cecilie Vestrheim Thomsen received the prize for best poster and Post.doc. Lobke Gierman received third place in the category best oral presentation.

Article in Placenta:   Toll-like receptor profiling of seven trophoblast cell lines warrants caution for translation to primary trophoblasts

 

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Filed under Cardiovascular, Inflammatory and Immune System, NTNUmedicine, Reproductive Health and Childbirth, Research

Harald Stenmark receives Møbius award

Harald Stenmark

Harald Stenmark

Professor Harald Stenmark,  has received this year’s “Møbius award”, the Research Council of Norway’s annual prize for excellent research. Stenmark is director of the Centre for Cancer Biomedicine at UIO and Professor II at the  Centre of Molecular Inflammation Research, CEMIR.

The award is granted on the basis of documented results, and is intended to encourage further research activity. The award amounts to 1 mill. NOK and is distributed Wednesday September 23rd in Oslo Konserthus.

Congratulations to Professor Stenmark!

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