Researchers find new method to treat wounds and skin infections
- Scientists from the University of Calgary, Canada, have discovered a promising new approach to treating bacterial skin infections.
- The research showed that monocytes alone are capable of facilitating faster wound healing.
- The researchers' next step is to better understand how immune cells like neutrophils function during infection.
Researchers have discovered a promising new approach to treating bacterial skin infections.
A team of scientists from the University of Calgary, Canada, revealed new insights which could lead to advancements in the treatment of bacterial infections and wounds, according to a study published in Nature science journal on Friday.
"It is exciting that we have made a fundamental discovery that could improve infections and tissue repair in humans, especially hard-to-treat cases," said the study's first author Dr. Rachel Kratofi in the press release. "Translating our research from bench to bedside will require many more experiments and involve a model more closely related to human disease."
The research showed that monocytes alone are capable of facilitating faster wound healing. Monocytes contribute to wound healing by regulating leptin levels and blood vessel growth. They also produce ghrelin, a hormone that aids in wound healing.
Historically, researchers believed that neutrophils and monocytes (white blood cells) were both recruited to clear bacteria from an infected site on the skin. When these cells work together, they serve as our bodies first line of defense against the immune system.
The connection between metabolic hormones and tissue repair
Ghrelin is produced by the stomach when you are hungry, whereas leptin is produced by fat cells after you eat a meal and feel full.
This ghrelin-leptin balance has long been recognized as important for metabolism and diet. Still, its relationship to immune mechanisms and tissue repair has been unknown until now.
Kratofil was able to visualize the immune response to Staphylococcus aureus (S. aureus) bacteria in an animal model using intravital microscopy, which allows observation of live cells and is a specialization of the university's Kubes Lab.
S. aureus is a germ commonly found on the skin or in the noses of healthy people. It can cause a variety of skin and tissue infections, including abscesses, boils, pneumonia, and endocarditis, a potentially fatal inflammation of the inner lining of the heart's chambers and valves.
Following infection with S aureus, the body recruits healthy immune cells, neutrophils, and monocytes. Monocytes aid in tissue repair while neutrophils clear bacteria. Without monocytes, leptin production increases, causing blood vessel growth in the infection. Ghrelin inhibits leptin-induced excess blood vessel growth, resulting in tissue repair.
Study results show a 'paradigm shift'
"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," Kratofi explained.
The discovery "opens the door to the introduction of metabolic hormones (ghrelin and leptin) in immunology and microbiology," according to Kubes Lab's principal investigator and his research group.
"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," said Kubes.
The researchers' next step is to better understand how immune cells like neutrophils function during infection. They are particularly curious about how infections are cleaned from neutrophils and whether neutrophils do other tasks besides clearing bacteria.
The interdisciplinary work of this research team is the result of 133 independent experiments conducted in collaboration with the labs of Dr. Keith Sharkey, Ph.D. (Snyder Institute, Hotchkiss Brain Institute (HBI)), Dr. Jeff Biernaskie, Ph.D. (HBI and Alberta Children's Hospital Research Institute), and researchers from University Hospital Regensburg, Germany, and Texas A&M University.
Canadian Institutes of Health Research has funded the study.
During infection, inflammatory monocytes are thought to be key for bacterial eradication, but this is hard to reconcile with the large numbers of neutrophils that are recruited for each monocyte that migrates to the afflicted tissue and the much more robust microbicidal functions of the neutrophils. However, unlike neutrophils, monocytes have the capacity to convert to situationally specific macrophages that may have critical functions beyond infection control1,2. Here, using a foreign body coated with Staphylococcus aureus and imaging over time from cutaneous infection to wound resolution, we show that monocytes and neutrophils are recruited in similar numbers with low-dose infection but not with high-dose infection and form a localization pattern in which monocytes surround the infection site, whereas neutrophils infiltrate it. Monocytes did not contribute to bacterial clearance but converted to macrophages that persisted for weeks after infection, regulating hypodermal adipocyte expansion and production of the adipokine hormone leptin. In infected monocyte-deficient mice, there was increased persistent hypodermis thickening and an elevated leptin level, which drove overgrowth of dysfunctional blood vasculature and delayed healing with a thickened scar. Ghrelin, which opposes leptin function3, was produced locally by monocytes, and reduced vascular overgrowth and improved healing post-infection. In sum, we find that monocytes function as a cellular rheostat by regulating leptin levels and revascularization during wound repair.
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