Wellcome Trust Research Round-up: 29/09/14

Our fortnightly round-up of research news from the Wellcome Trust community…

Immune system of newborn babies is stronger than previously thought

The immune system of a newborn baby, although very different to an adult’s, may still be able to mount a strong immune defense, according to new findings that go against the received wisdom on this topic.  

The study, published in Nature Medicine and funded by the Wellcome Trust, found that the immune T cells of newborn babies may have the ability to trigger an inflammatory response to bacteria. Up to now, it was generally believed that babies have an immature immune system that doesn’t allow this. Although babies need to protect themselves from the harmful pathogens they are exposed to from birth, it was thought that their T cells were suppressed to some extent to prevent inflammatory damage to the developing child.

Now, a team at Kings College London has discovered that whilst T cells in newborn babies are largely different to those in adults, it is not because they are immunosuppressed. Rather, they manufacture a potent anti-bacterial molecule known as IL8 that has not previously been considered to be a major product of T cells, and that activates neutrophils to attack the body’s foreign invaders.

Deena Gibbons, lead author at King’s College London, says: “We found that babies have an in-built anti-bacterial defense mechanism that works differently to adults, but nevertheless may be effective in protecting them. This may also be a mechanism by which the baby protects itself in utero from infections of the mother. The next stage of our work will be to better understand the pathways that result in the immune cells of newborns being so different to those in adults.”

Statins associated with modest increases in weight and diabetes risk

The mechanism by which statins increase the risk of type 2 diabetes has been investigated in a large-scale analysis from an international team led by researchers from UCL and the University of Glasgow, using information from genetic studies and clinical trials.

Published in The Lancet, the work received support from a number of funders including the Wellcome Trust, the Medical Research Council, British Heart Foundation, Rosetrees Trust and National Institute for Health Research University College London Hospitals Biomedical Research Centre.

Among nearly 130 000 participants from clinical trials that previously tested the effect of statins on heart disease and stroke, those assigned statins vs. placebo, or higher vs. lower doses of statins, were noted to have a small increase in the risk of developing type 2 diabetes, of about 12% over a four-year period, and also to gain an excess of 240g (around half a pound) in weight.

“Weight gain is a risk factor for diabetes which might help explain the small increased risk of diabetes observed in people taking statins”, explains co-lead author Dr David Preiss of the University of Glasgow Institute of Cardiovascular and Medical Sciences.

Statins work by reducing the efficiency of a liver enzyme involved in cholesterol production, which causes liver cells to trap more low-density lipoprotein (LDL-) cholesterol from the bloodstream, reducing its circulating level. This mechanism is thought to underlie the efficacy of statins in lowering the risk of stroke and heart disease.

HIV-infected individuals receiving therapy are still susceptible to TB disease

People infected with HIV, but who are stable and taking a combination of potent antiretroviral drugs (known as ART), are still more susceptible to developing TB disease than those who are not HIV-infected because of problems with TB-specific immune responses in their lungs, according to a new study.

TB is an opportunistic infection which commonly infects and kills people who have HIV. A new study, conducted by researchers at the Malawi-Liverpool Wellcome Trust Clinical Research Programme, explains why people taking ART who have undetectable concentration of HIV viruses in their blood and a high T cell count (indicating a good response to ART and a strong immune system) are still susceptible to developing TB disease.

The study, published in the American Journal of Respiratory and Critical Care Medicine, examined blood and lung samples from 35 HIV-uninfected, 25 HIV-infected ART-naïve (those who were not taking ART), and 50 HIV-infected ART-treated adults.

They found that immune cells found in the lungs called ‘alveolar macrophages’ and T cells that respond specifically to the presence of the TB-causing bacteria or its proteins do not work properly in HIV-infected adults who have taken ART for less than four years, partly explaining why they are susceptible to developing TB disease.

Dr Kondwani Jambo, a postdoctoral fellow funded by the Malawi Health Research Capacity Strengthening Initiative (HRCSI), which is part-funded by the Wellcome Trust, and Dr Henry Mwandumba, a Wellcome Trust Intermediate Clinical Fellow, are among the authors of the study. Dr Mwandumba said: “These findings underscore the need for strategies to augment ART to improve lung immune cell function and reduce the incidence of TB. The use of vaccines that promote repopulation of the lungs with TB-specific immune cells and the use of preventive TB treatments, especially during the early years of ART when HIV-infected individuals are most vulnerable, ought to be considered.”

Image credits: Newborn baby – Anthea Sieveking, Wellcome Images; Model of human enzyme inhibited by statins – T. Greenhough & A. Shrive, Wellcome Images; HIV particles – R. Dourmashkin, Wellcome Images.