A group of researchers from Washington University in St. Louis, Agios Pharmaceuticals and ITMO University has discovered new metabolic mechanisms that regulate macrophage polarization - the unique ability of these immune cells to change their specialization depending on the required task. The research opens new possibilities for the development of a new class of drugs based on controlling the metabolism of immune cells. The results were published today in the Immunity journal.
One of the key properties of macrophages is their ability to assume different states in accordance with the environmental factors. For example, resident macrophages (M0) can undergo classical activation and transform into proinflammatory macrophages (M1) that by all means seek to destroy pathogens.
There exists, however, an alternative activation procedure, wherein macrophages acquire an anti-inflammatory healing function (M2). Understanding these processes is extremely important for understanding the immune system as a whole as well as for fighting autoimmune diseases.
Macrophage polarization is accompanied by changes on both transcriptional and metabolic levels. Activation significantly alters the expression of some genes and the concentration of used and produced compounds. While some aspects of activation are known, until recently, the big picture remained elusive.
To study macrophage polarization, the scientists developed the method of non-targeted analysis of metabolic changes based on data obtained from the simultaneous use of RNA sequencing and high-throughput mass spectrometry of metabolites. The researchers combined the data on the basis of the network of biochemical reactions, which allowed them to identify the most significant of the ongoing reactions.
The final set of reactions revealed unknown metabolic mechanisms associated with macrophage polarization. Based on this information, the scientists determined the most probable metabolic pathways that manifest themselves in classical and alternative activations.
The pathways were confirmed using 13C and 15N isotope labeling and pharmacological inhibition experiments. One of the new mechanisms described in the work is the dependence of alternative macrophage activation on glutamine concentration in the environment, which regulates the activity of TCA cycle, and the synthesis of UDP-Glc-Nac - the compound necessary for post-translational protein modification.
"We developed a method of simultaneous analysis of metabolic and transcriptional data. The method proved to be effective and, most importantly, yielded a concrete biological result. Now we continue to improve the method and apply it to other biological tasks such as studying cancer metabolism," says Alexey Sergushichev, PhD student at Computer Technologies Department of ITMO University.
In the long run, the ability to regulate pro- and anti-inflammatory activity can lead to the creation of a new class of drugs based on controlling the metabolism of immune cells. For the first time, macrophage polarization was described in such detail and on such a scale. The work made it possible not only to reveal new regulatory mechanisms of polarization, but also identify and describe the global restructuration of metabolic pathways during polarization. The researchers hope their work will give new impetus to the investigation of pharmacological potential of polarization regulators, which also represents the next step in the collaborative work of the group.
The press office of ITMO University thanks Alexey Sergushichev and Maxim Artyomov for their help in preparing this press release.
Dmitry Malkov | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy