Possible new vaccines against bacterial infections
EU-funded research has shown how skin cells can warn our immune systems of an impending bacterial attack, offering the potential for vaccines against antibiotic-resistant infections that could save lives.
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The Staphylococcus aureus (S. aureus) bacterium is a major threat to public health. It is responsible for a wide range of infections from minor skin problems such as boils to life-threatening conditions such as endocarditis in the heart, pneumonia in the lungs and sepsis in the blood.
Particularly worrying is the methicillin-resistant Staphylococcus aureus (MRSA) strain, which is resistant to antibiotics and a major cause of hospital infections. This is one reason why S. aureus was designated a priority pathogen by the World Health Organization in 2017, placing it among 12 families of bacteria that pose the greatest threat to human health and for which new antibiotics or other treatments are desperately needed.
The EU-funded METAPATH project worked on one such new treatment by taking a close look at our skin and seeking clues not for a new antibiotic but rather a vaccine against S. aureus.
Staphylococcus is at its most dangerous when it gets inside the body, into our blood and organs. However, to get there it must first pass through our skin and our skin is a wonderful protective barrier, both for chemicals and pathogens, says METAPATH scientist Sandrine Henri of Frances Institut National de la Santé et de la Recherche Médicale (INSERM).
The skin has its own ways of destroying harmful bacteria such as S. aureus. We are looking at how mouse skin deals with infection and have found evidence that may lead to effective vaccines in the future.
Forewarned is forearmed
The research discovered that when S. aureus lands on the skin, certain cells are activated to process the required antigen to combat it. These dendritic cells then go through the lymphatic system into the lymph nodes, which play a vital role in immune response. There they interact with T-cells, also known as pathogen killers, and show a copy of the antigen to them.
This means that if the S. aureus strain passes inside the body, the internal immune system has been forewarned and can rapidly adapt itself to fight the spread of infection. Most importantly, the researchers found that, even if S. aureus doesnt penetrate the skin, these T-cells retain a memory of the strain. This memory is where the potential for a vaccine lies.
In this basic research we investigated the link between the bodys innate immune system and its adaptive immune counterpart, says Henri.
The innate system includes the skin and the bacteria found on it. These form a non-specific defence system, the first line of defence. The adaptive immune system sits in the lymphoid system and includes cells that can adapt themselves to fight particular threats.
Dendritic cells act as messengers between the innate and adaptive systems. The researchers also found that mice whose skin had been colonised once with S. aureus were more resistant to a second infection down the road. This was the clue for a memory function, which further trials showed to be initiated by the dendritic cells in the skin.
Henri received funding from the EUs Marie Skłodowska-Curie fellowship programme to carry out research at the National Institutes of Health in the United States. There, she worked with the team of Yasmine Belkaid an award-winning world expert in infections and their causes. The cooperation continues to this day, Henri says.
METAPATH involved very basic research into cell biology and how immune systems work, Henri says. The discovery of a memory function is exciting and holds the tentative promise of vaccine-based immunotherapy approaches to S. aureus and perhaps other pathogens. However, we still have some way to go and much research to be done.