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.
Reforming lung tissue to fight the flu
In response to a flu infection, lung tissue that isn’t normally involved in the immune system can be remodelled to form emergency immune centres, helping to fight off the infection. These lung-based immune hubs, known as germinal centres, produce antibodies that can recognise a broad range of flu strains – something current flu vaccines are not able to do. Now, in a step towards more effective vaccines, research published in the Journal of Experimental Medicine has revealed the process which causes the lungs to form germinal centres.
Infected lung cells produce interferon, a chemical messenger that signals where immune cells are needed. B cells (the immune cells responsible for making antibodies) respond to the call and make their way to the lungs. This drives the formation of the germinal centres through the co-ordination of many immune cell types, creating the ideal microenvironment for producing the broadly protective antibodies. Researchers were able to replicate this chain of events in mice by administering interferon and another molecule, triggering germinal centres to form even in healthy animals. It is hoped that adding compounds similar to interferon to the flu vaccine could prove a useful improvement, encouraging germinal centres to form in the lungs and producing cross reactive antibodies.
Dr Michelle Linterman, BSI member and research group leader, explained the significance of the study: “One important function of germinal centres when responding to infection is that they support the creation of cross-reactive antibodies that can confer wider protection.
“Being able to exploit this would be extremely beneficial in the case of the annual influenza vaccination where the vaccination is developed against the likely prevalent strain. In the case of vaccinating against one type of influenza virus, wider protection against other types of influenza strains would reduce infections and thereby improve health.”
Read the press release here.
Read the full article here: Denton A. et al. 2019 Journal of Experimental Medicine DOI: https://doi.org/10.1084/jem.20181216
Master regulator keeps control of whipworm infection
Whipworms are a type of parasitic roundworm that live in the cells lining the gut of their host. The gut is also home to millions of bacteria known as the microbiota, which usually work with the immune system to keep the infection under control, eventually getting rid of the worm. New research, published in PLOS Pathogens, reveals that regulating the delicate balance between the gut, its bacteria, the immune system and the worm is reliant on the signalling of a single master regulator.
Interleukins are the chemical messengers of the immune system, and act in harmony with the microbiota to keep opportunistic bacteria in check and prevent tissue damage. However, in mice lacking interleukin receptor genes, the careful equilibrium is disrupted. In this scenario, the whipworms alter the microbiota composition which in turn changes the way in which the immune system responds. The cells lining the gut are broken down by uncontrolled inflammation, providing an easy escape route for bacteria to surge into the liver – leading to organ failure and death. The study showed that interleukin-10 receptor signalling was crucial for promoting the body’s own defences against the worm and ultimately the survival of the mouse.
Professor Richard Grencis, a BSI member from The University of Manchester, commented: “This is the first study revealing the master role of interleukin-10 receptor in regulating the response to whipworm, and controlling the microbiota. We discovered the absence of this crucial signalling pathway leads to disturbed microbiota and uncontrolled inflammation that destroys the gut lining allowing microbes to invade and cause liver failure.”
Read the press release here.
Read the full article here: Duque-Correa M. et al. 2019 PLOS Pathogens DOI: https://doi.org/10.1371/journal.ppat.1007265
Scientists uncover body’s satnav for regulatory T cells
Regulatory T cells (Tregs) are specialised immune cells which are important for keeping the immune system under control. They can be found all over the body, and are uniquely adapted to perform slightly different jobs depending on the tissue they end up in. In a study published recently in Immunity, researchers have identified key details of the satnav system which ensures Tregs arrive at their final destination, in the hope of harnessing this to target treatments to specific areas of the body.
Researchers from the Wellcome Sanger Institute examined the gene activity of 35,000 individual mouse Tregs to look for differences between cells from skin, colon and lymph tissue (where T cells originate and mature). They found that Tregs collected from each tissue environment had slight differences in gene activity, which developed as they moved between tissues. These adaptations allow the Tregs to follow cues, such as chemokines and other cell-surface receptors, to the correct location in the body. Importantly, when researchers examined Tregs in humans, they found the cells had similar tissue-specific molecular identities to their mouse counterparts.
Dr Sarah Teichmann, corresponding author, said: “This is the most comprehensive study ever performed of single cell RNA sequencing of T regulatory cells across tissues. Not only does it help us understand the immune system within a tissue, it also reveals which regulators and receptors are expressed in each tissue. This could help researchers learn how to manipulate potential therapeutic T cells in the future, to design them for specific locations in the body and target exactly the right tissue needed.”
Read the press release here.
Read the full article here: Miragaia R. et al. 2019 Immunity DOI: https://doi.org/10.1016/j.immuni.2019.01.001