New defensive mechanism against bacterial wound infections

Wound inflammation which results in impaired wound healing can have serious consequences for patients. Researchers from Charité -- Universitätsmedizin Berlin have discovered a new defensive mechanism which enables our skin to actively kill bacteria. Central to this mechanism is a cellular messenger molecule known as 'interleukin 6', whose mode of action may be used in the future to prevent wound infections.

Skin wound colonization by bacteria or other pathogens can lead to severe inflammation. In the worst cases, this can result in septicemia or amputation. Prompt treatment is therefore essential. However, growing numbers of bacteria developing antibiotic resistance have resulted in treatment options becoming increasingly limited.

The researchers investigated the hypothesis that the skin's host defense against pathogens might include 'mast cells', a type of defensive immune system cell which is known to play a major role in allergies. Mast cells are responsible for the body's response to otherwise harmless substances, producing symptoms such as runny nose or itching. However, researchers suspect that their role goes beyond this mediation of abnormal immune responses, with some results suggesting that they play a role in our body's defense against pathogens.

Using an animal model, the researchers studied the effects of an absence of mast cells on wound healing after infection. The researchers observed that, on day five after infection, the total number of bacteria present in the wound was 20 times higher if mast cells were absent. This resulted in the infected wound taking several days longer to close. According to the researchers' findings, the mast cells' bacteria-killing effect is a product of the release of the messenger molecule interleukin 6. This molecule stimulates cells within the superficial layer of the skin, prompting them to release 'antimicrobial peptides', short protein chains which kill bacteria, viruses and fungi.

The study demonstrated the nature and extent of mast cell involvement in the skin's host defense mechanism against bacteria. Exploiting their knowledge of interleukin 6 and its key function, the researchers found that the application of interleukin 6 to the wound prior to infection resulted in an improved defense against bacteria, even in animals with intact immune systems.

The researchers were also able to replicate this effect in human tissue.

See:

C. Zimmermann, D. Troeltzsch, V. A. Giménez-Rivera, S. J. Galli, M. Metz, M. Maurer, F. Siebenhaar. Mast cells are critical for controlling the bacterial burden and the healing of infected wounds. Proceedings of the National Academy of Sciences, 2019; 201908816 DOI: 10.1073/pnas.1908816116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology