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Immunology Update - March 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.

Mechanism behind why allergies are more common in developed countries discovered

The hygiene hypothesis is the idea that the lack of exposure to a wide variety of micro-organisms in childhood increases the chances of developing allergies. Countries with a high incidence of worm infections have a low incidence of allergy, but so far there has been little concrete molecular evidence for why this is the case. Now, a new study published in the journal, Immunology, has discovered a novel molecular mechanism that supports the hygiene hypothesis.

The researchers found that rabbit antibodies raised against proteins on parasitic worms also reacted to several proteins in peanuts, and six other plant extracts.  Although the exact relationship is unclear, this work goes some way towards supporting the hygiene hypothesis. The team think that antibodies produced in response to a worm infection could block the immune system from reacting adversely when it encounters new substances like peanuts, thus reducing the incidence of allergy. This work could form the basis of new immunotherapies to treat allergies.

Author and BSI member Professor Mike Doenhoff from the University of Nottingham added “It may sound strange that peanuts and worms have anything in common that could cause the immune system to generate the same response. However, our work indicates that proteins from these two seemingly very different organisms actually have identical markers on them, meaning the immune system views them in the same way and targets them with similar antibodies.”

Read the press release here

Read the full paper here: Igetei et al. 2017 Immunology doi: 10.1111/imm.12711

New class of drugs for treating human whipworm

Human whipworm is a neglected tropical disease and current treatments, originally developed for livestock, have a low success rate in people. A recent interdisciplinary project, from the Universities of Manchester, Oxford, and University College London, has identified a novel class of anthelmintic drugs called dihydrobenzoxazepinone. These compounds were found to kill adult worms far more effectively than current treatments, and were also effective against the eggs, which are notoriously resistant to extreme temperature changes and UV light. The researchers hope to develop these compounds into an effective treatment for human infection, as well as a spray product to tackle whipworm eggs in the soil of endemic areas. Both are important steps forward on the path to eradicate this disease.

BSI member Professor Kathryn Else said: “Although we rarely see whipworm infection in the UK, it is a serious and damaging problem in many parts of the world and if we can develop this treatment, the lives of many people could be improved.” This work was published in PLOS Neglected Tropical Diseases.

Read the press release here

Read the full paper here: Partridge et al. 2017 PLOS Neglected Tropical Diseases doi:10.1371/journal.pntd.0005359

Genetic variant linked to overactive inflammatory response

The gene interferon-induced transmembrane protein 3 (IFITM3) codes for a transmembrane protein on cells, also called IFITM3, that plays a key role in the immune system’s defence against viruses. Some immune systems are known to overreact to viral infections, and variants in the gene IFITM3 are already known to influence how sensitive people are to the influenza virus. A new study from the University of Cardiff, published in the Journal of Clinical Investigation, has revealed that this gene also plays a role in controlling the scale of the inflammatory response to a viral infection.

The researchers used a mouse model of cytomegalovirus to determine the cellular protective role IFITM3 plays during viral infection. Studying mice deficient in IFITM3, the researchers found these mice exhibit uncontrolled production of inflammatory cytokines such as IL-6, which resulted in a loss of natural killer cells and an impaired response to the virus.

BSI member Dr Ian Humphreys from Cardiff University's School of Medicine said: "Now we know that genetic make-up influences how the immune system copes with infections, not only by influencing how the body controls an infection but also by controlling how strongly the body's immune system reacts, we can design therapeutic strategies for individuals who are seriously ill with infections, which are tailored to the individual based on their genetic profile."

Read the press release here

Read the full paper here: Stacey et al. 2017 Journal of Clinical Investigation doi: 10.1172/JCI84889

A new role for an old immune cell discovered

Gamma Delta (γδ) T cells are an unconventional subset of T cells that have been preserved through over 450 million years of evolution. These were originally thought to play an innate ‘natural born killer’ role in immune defence but a new study from the University of Birmingham has revealed a novel ‘adaptive’ function for γδ T cells.

The researchers found that γδ T cells could generate immunological memory against previous infections and cancerous targets. Immunological memory is a process that vaccines exploit, and because γδ T cell memory works in a slightly different way to conventional T cells, they represent a novel opportunity for vaccine design. Further work is needed to understand how γδ T cells recognise their targets because they are not restricted to the classical MHC-complex system of conventional T cells.

Lead author and BSI member, Professor Ben Wilcox said: "We are working with other partners to understand exactly how these cells recognise signs of abnormality in infection and cancer, focussing on human cohorts. This knowledge will be crucial to help us build on the current study and explore how to develop new cell therapies and vaccines that exploit Gamma Delta T cells." This work was published in Nature Communications.

Read the press release here

Read the full paper here: Davey et al. 2017 Nature Communications doi: 10.1038/NCOMMS14760