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Immunology Update - October 2017

Welcome to the next installment of our regular update where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past few weeks.


Worming a way towards a cure for asthma

Helminth (worm) infection has long been acknowledged to offer protection against allergic diseases. In an attempt to prolong their stay within their host, the parasites release immunomodulatory proteins to subvert the immune system. This diversion, however, also helpfully diminishes allergic responses.

“This has led to the proposal that deliberate self-infection with parasites could help asthma; however, this can be uncomfortable and impractical, as well as potentially causing other health issues. We have always believed that a better technique would be to identify how parasites prevent asthma, so that new parasite-inspired treatments can be developed,” says Dr Henry McSorley, Chancellor’s Fellow, MRC Centre for Inflammation Research and BSI member.

Dr McSorley and Professor Rick Maizels led a team of researchers who identified H.polygyrus Alarmin Release Inhibitor (HpARI) , an immunomodulatory protein, secreted by the parasite Heligmosomoides polygyrus. The paper, published in Immunity, explains that administration of recombinant HpARI suppresses allergic immune responses and the development of allergic airway inflammation in mice, through sequestering a cytokine key to initiating the immune response. Using both mice and human lung homogenate, it was demonstrated that the protein binds both IL-33 and DNA, and thus prevents the cytokine’s escape from necrotic cells, and consequently withholds the activating stimuli for the immune cells (ILC2s, eosinophils and macrophages) that mediate allergic airway inflammation. This research holds potential for the development of a cure for wide range of allergic diseases from asthma and COPD to food allergy, atopic dermatitis and age-related macular degeneration.

Read the full press release here.

Read the full paper here: Osbourn et al. 2017 Immunity 47 739–751 DOI: https://doi.org/10.1016/j.immuni.2017.09.015

 


Novel target for a potential cystic fibrosis therapy

Worldwide, it is estimated that more than 70,000 people are living with cystic fibrosis and, on average, only half of those suffering with disease will live beyond the age of 40.  Although the recessive genetic disorder affects numerous different organs, the majority of fatalities are due to lung infections. The well-known symptom of cystic fibrosis, a build-up of thick mucus, along with an impaired ability to kill bacteria and an unrestrained inflammatory response, are the main underlying causes of this.  

A new study by a team of scientists from the Medical Research Council Centre for Inflammation Research at the University of Edinburgh have uncovered neutrophil apoptosis as a novel target for future therapies.

Neutrophils are an important member of the innate immune system, direct killers of bacteria and recruiters of other immune cells. CFTR, the gene faulty in those suffering from cystic fibrosis, has been shown to have a wide range of roles within the immune system. This study, through a series of experiments working with neutrophils taken form the blood of both people and pigs with cystic fibrosis, reveals that the protein’s dysfunction causes delayed neutrophil apoptosis and thus prolonged survival of the immune cells in cystic fibrosis. In compensation, an alternative form of programmed cell death, NETosis more prevalent.

This creates two problems. Firstly, prolonged neutrophil survival hinders infection and inflammation resolution as neutrophil apoptosis is a protective mechanism. Secondly, NETosis involves the release of NETs (neutrophil extracellular traps) composed of DNA and associated proteins, in a final attempt to kill bacteria. However, these NETs also stimulate macrophages, which have already been shown to be hyper-responsive in cystic fibrosis patients, to induce an inflammatory response. In light of their findings, published in Thorax, the team proposed the use of cell cycle inhibitors to induce apoptosis.

Dr Donald Davidson, Senior Research Fellow at the MRC Centre for Inflammation Research and Chair of the BSI’s Inflammation Affinity Group, said: “How our immune cells die can be as important as how they function in life for protecting our bodies. This study shows that encouraging them to die quietly can help to prevent damaging inflammation.”

Read the full press release here.

Read the full paper here:  Gray et al. 2017 Thorax  DOI: 10.1136/thoraxjnl-2017-210134

 


Dengue virus could help treat Zika infection

New research, from a team of scientists at Imperial College London and Washington University in St Louis, has uncovered the potential of antibodies taken from a person infected with Dengue virus may be effective in treating Zika infection in mice.

Zika is a mosquito-borne virus that has caused devastation in the past few years, with infection of pregnant mothers resulting in babies with congenital abnormalities. Dengue and Zika are related viruses, both from the Flaviviridae family, but it now appears they share more than just the family traits of a symmetrical shape and nucleic acid type. The team demonstrated that neutralising antibodies specific to the Dengue virus E-dimer epitope (EDE) worked to protect against Zika virus too. Administration of the antibody after Zika infection reduced the viral load in the brain and testes in mice. It also drastically reduced the death rate of pups born to infected mothers.

“This paper shows for the first time that antibodies we had previously found to be effective against Dengue potently protect against Zika virus in mice and can treat the early stages of infection,” says Professor Gavin Screaton, Dean of the Faculty of Medicine at Imperial and senior author of the paper published in Nature Immunology. “This group of antibodies is unique in being able to target Dengue and Zika. The next step is to see whether they are effective in larger animal models, and potentially even humans.”

The hope is to develop therapies that could control both viral diseases, with a vaccine based on the shared target of these antibodies now appearing like an exciting possibility.

Read the whole press release here.

Read the whole paper here: Fernandez et al. 2017 Nature Immunology DOI: 10.1038/ni.3849