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.
Immune cells with a sweet tooth
Macrophages are immune cells that can engulf and digest pathogens to prevent them causing disease. Control of the immune response is important to prevent inflammatory disease that could cause damage, particularly for chronic conditions such as asthma. New research led by The University of Manchester has found that in mice these cells respond to lung sugar levels, in a way that would one day be used in the clinic.
The study, published in Nature Immunology, showed that macrophages in the lungs of mice responded poorly to interleukin-4 (an inflammatory molecule important in allergic disease), compared with macrophages from elsewhere in the body. When these cells were taken outside the body and provided with glucose as an energy source, they became more responsive. There is generally less glucose in the lungs than in the blood. It is possible that helping lung macrophages access more sugar may help activate the immune response in the lungs.
Professor Andrew MacDonald, who led the study, said, “During inflammation of the type seen in asthma and parasitic worm infection it appears that glucose, and use of glucose, controls macrophage activation in the lungs. This study reveals the crucial role sugar plays in immune cells in the airways of mice, but in terms of clinical application in people, it’s very early days, and a great deal more research needs to be carried out before any human treatments could be developed.”
Read the press release here.
Read the full article here; Svedberg F et al. 2019 Nature Immunology DOI: 10.1038/s41590-019-0352-y
HPV vaccination success
Human papilloma virus (HPV) is a sexually transmitted disease, where infection is a major risk for cervical cancer, the fourth most common cancer in women. Scotland introduced a vaccination programme in 2008, targeting girls aged 12–13. Screening at age 20 has shown a dramatic reduction in abnormal cells, an early sign of cancer. In work published in the British Medical Journal, the vaccine has been linked to an 89% drop in women with high-grade abnormal cells and a 79% reduction in low-grade abnormal cells. There is evidence that even unvaccinated young women have benefitted, through a process called herd immunity. Herd immunity is the level at which so many people are vaccinated, the virus cannot find a non-immune person to infect. Although the vaccine appears most effective in younger girls, a catch-up programme allowing vaccination at age 17 has also resulted in a 50% drop in abnormal cells.
Dr Tim Palmer, of the University of Edinburgh, says, “Our findings from Scotland suggest the HPV vaccine is working and will eventually reduce cervical cancer rates. This underpins the recent call for global action on cervical cancer from the World Health Organization.”
The researchers did not see any evidence of HPV finding a way around the vaccine, but rather concluded that the vaccine was highly cross-protective against multiple strains of HPV. These strains are implicated in 90% of cervical cancers in Scotland. There have been no serious adverse effects linked to the vaccine.
Read the press release here
Read the full article here; Palmer T et al. 2019 British Medical Journal DOI: https://doi.org/10.1136/bmj.l1161
Cholesterol controls T cell response
Research led by King’s College London has recently demonstrated a link between cholesterol metabolism and immune regulation. T-helper (Th) cells are immune effector cells that can respond to a wide range of pathogens. They must be tightly controlled to avoid host damage; one way the immune response is controlled is by causing Th cells to produce anti-inflammatory instead of pro-inflammatory molecules. Research published in Nature Communications shows that blocking cholesterol production in vitro with drugs such as statins can control this anti-inflammatory off switch.
The researchers found that an imbalance in cholesterol metabolism within joints increases the risk of developing rheumatoid arthritis. Historically, treatments used to control the immune system have largely focused on drugs that suppress the immune system, such as those used to prevent rejection of organ transplants or to suppress symptoms associated with rheumatoid arthritis. The team are now testing whether drugs that modify cholesterol, such as statins, could be re-purposed to either prevent chronic inflammation or to promote immunity against infection.
Dr Esperanza Perucha explained the impact of the results, “One of the biggest questions in immunology research is about understanding the way the immune system turns on and off. Understanding how this switch works then allows us to design therapies to boost or hinder the immune response.”
Read the press release here
Read the full article here; Perucha E et al. 2019 Nature Communications DOI: 10.1038/s41467-019-08332-9