The study elevates the role of monocytes in wound repair.

New research may lead to advancements in treating bacterial infections and wounds.

Monocytes alone are capable of facilitating faster healing of wounds. Monocytes help the healing process by regulating leptin levels and blood vessel growth during wound repair. They also produce ghrelin, a hormone that helps wounds heal more efficiently.

Ghrelin is produced by the stomach when you are hungry, and leptin — also a hormone — is produced by fat cells after you eat a meal and feel full. This balance between ghrelin and leptin has long been understood as critical to metabolism and diet, but until now, has not been known for its connection to immune mechanisms and tissue repair.

Using intravital microscopy, which allows observation of live cells and is a specialization of the Kubes Lab, the research team was able to visualize the immune response to Staphylococcus aureus (S. aureus) bacteria in an animal model.

After an S. aureus infection, the body recruits those helpful immune cells, neutrophils and monocytes. In the absence of monocytes there is increased leptin production, leading to blood vessel growth in the infection. The result can be delayed healing and scarring. In contrast, monocytes produce ghrelin at the infection site, which blocks the formation of excess blood vessel growth driven by leptin, leading to tissue repair.

The study is published in Nature.

“While translating our research from bench to bedside will require many more experiments and involve a model more closely related to human disease, it is exciting that we have made a fundamental discovery that could improve infections and tissue repair in humans, especially hard-to-treat cases,” says study author Dr. Rachel Kratofil, PhD,  a recent trainee in the Kubes Lab at the Cumming School of Medicine’s (CSM) Snyder Institute for Chronic Diseases at the University of Calgary in Calgary, Alberta, Canada, in a news release.

“This research is important because it indicates a paradigm shift challenging the current thinking that neutrophils and monocytes clear bacteria. Our study elevates the role of monocytes in wound repair,” explains Kratofil.

Principal investigator Paul Kubes, PhD, and his research team believe this study opens the door to introduce metabolic hormones (ghrelin and leptin) in the fields of immunology and microbiology.

“It will be interesting, for example, to see how ghrelin and leptin respond in other disease models such as sterile injury or cancer, and to learn how these processes are altered when a patient has multiple simultaneous diseases or conditions such as obesity and diabetes,” says Kubes.

Next steps

The next step for the researchers is to better understand the functions of immune cells such as neutrophils during infection. Specifically, they are interested in how neutrophils become cleared from an infection and whether neutrophils take on different functions in addition to clearing bacteria.

IMAGE: RACHEL KRATOFIL 

CREDIT: RACHEL KRATOFIL