Boosting the body's natural response to infections

As part of the SHIELD consortium, Simone's research aims to find ways to boost the body’s natural immune response to bacterial infections, in order to reduce the overall use of antibiotics used to treat people who get infected by bacteria. This is because the more antibiotics that are used, the greater the chance that the bacteria will become resistant to them – resulting in these medicines becoming ineffective at destroying bacteria. This makes it harder to treat common infections, and routine medical procedures can become very high risk.

Developing strategies that boost our immune systems could help to protect us from against all sorts of bacteria (and maybe viruses or fungi too), whereas currently each antibiotic can only be used with certain types of bacteria. This could also help to treat the more difficult to tackle infections, like those caused by bacteria which are already resistant to some of our antibiotics – including MRSA (named methicillin (an antibiotic) resistant Staphylococcus aureus).

Simone works on white blood cells called neutrophils. Neutrophils are type of immune cell, specifically a granulocyte - which means you can see granules (like sugar granules) in these cells when you look at them with a microscope. We have more neutrophils than any other immune cell in our bodies and they are critical in the defence against infection. Neutrophils can also be described as phagocytes; this means they engulf (eat) invading microbes like bacteria to prevent them from harming the body.

In this picture we can see neutrophils (red and blue) after they have phagocytosed, “eaten”, Staphylococcus aureus (green dots).

Neutrophils circulate in your bloodstream, mixed in together with other components of the blood like red blood cells and plasma. One of the key parts of Simone’s work is isolating neutrophils from the blood and growing them with bacteria, to see how neutrophils generate the energy required to engulf and kill harmful bacteria.

This is important, because neutrophils have developed highly specialised ways of generating energy that allows them to function in the tissues where oxygen and nutrients are limited. By understanding this metabolic specialisation, Simone aims to identify new ways to regulate neutrophil anti-microbial functions in patients.

Behind the science - Simone Arienti

What is your favourite fact about neutrophils?

"Neutrophils are extremely special cells, and they are our best allies when it comes to fight an ongoing infection. They are surprisingly powerful cells with a broad set of “antimicrobial weapons”. However, their great potential to eliminate invading bacteria needs to be tightly regulated to prevent bystanding damage to healthy host tissues. I believe that to finely tune and boost neutrophil responses while reducing potential associated “collateral damage” is possible and this will play an important role in our fight against AMR."

Do you think your research is applicable outside of AMR research?

"Boosting a controlled immune response has also the advantage to be beneficial to a broad variety of situations beyond reducing the risk of selecting antimicrobial resistant bacteria. For instance, it might help to bolster immune-depressed individuals, or it might improve symptoms of patients with recurring infections, exemplified for example by patients which chronic lung disease. Importantly, it might also be applicable to cancer patients to hopefully foster an immune response that would work with current therapies and help overcoming the downside effects of cancer treatment such as chemo-/radiotherapies."

Why did you choose this AMR Training Programme?

"I chose this PhD Training Programme in AMR because I am fascinated by the immune system: how it works, how it responds and changes, and how it remembers after years and years. During my undergraduate studies at the University of Genoa (Italy) we discussed the problem of AMR, and I felt this huge problem was generally overlooked. Therefore, when the opportunity to couple my research interests with a problem that I felt so important presented, I decided to take the challenge of studying this problem and after almost 4 years I am still completely glad about the route I took."

"During this time, I met and became friends with the other students on the Training Programme, and I learned about their projects. It is thrilling to know that every single one of us is somehow contributing to tackle this world-wide problem and hopefully our research will have an impact on patients and will help others to overcome knowledge gaps."