Inflammation is the body’s natural response to injury and infections. It promotes healing through immune cell activation to target bacteria and other infections, but also allows for tissue repair. When the body experiences a physical injury or infection, an immune response is elicited. This immune response is comprised of many different cell types and proteins, which attract more cells to the site of injury. The first few cells to respond to infection include macrophages, neutrophils, and dendritic cells, which are all part of the innate immune response. Innate immunity works to clear any minor infections or abrasions but activates the adaptive immune response to specifically target cells that go unnoticed by innate cells. Short-term or “acute” inflammation is healthy as well as necessary for healing. Alternatively, chronic inflammation can dysregulate the immune system and is a common characteristic of many diseases, including cancer.
While inflammation was first described by the Ancient Romans, there is still much unknown about the inflammatory process in relation to healing. A recent report in Nature, by Dr. Kodi Ravichandran and others, demonstrate how a form of cell death can promote healing and tissue repair. Ravichandran is Professor and Chair of the Department of Microbiology and Immunology at the University of Virginia in Charlottesville, Virginia. His work focuses on the mechanism of cell death and cell clearance during normal tissue healing. His lab also actively investigates tumor cell death and how cancer can influence how the body clears dead cells.
The cells in our bodies are constantly going through life cycle phases. Consequently, many cells are dying while new ones are being generated. There are multiple ways in which cells die, including the process known as pyroptosis. This form of cell death is caused by significant inflammation that leads to tissue damage as the immune system tries to clear infections. Although cell death through pyroptosis is caused by inflammation, the process of cell death is also promoting inflammation. This positive feedback loop drives inflammation through the release of proteins. However, other molecules that promote wound healing are also released through pyroptosis.
Ravichandran and his team used lab techniques and animal studies to determine that pyroptotic cell molecule release influences the function of nearby cells. In this context, pyroptosis promotes inflammation, but also counters it by activating surrounding cells to begin healing the wound or infection. The team call the bulk of secreted molecules from these dying cells the “pyroptotic secretome”. Interestingly, the major wound-healing molecule the team detected in the pyroptotic secretome included prostaglandin E2, which plays a role in tissue regeneration.
This discovery is paradigm shifting because it was previously unknown that these dying cells had any role in wound healing. Ravichandran and his team have uncovered a previously unknown mechanism that could help improve tissue repair treatment and therapy against chronic inflammation in diseases, such as cancer. Overall, this work provides foundational knowledge on a process humankind has been familiar with for centuries. Physicians can now better understand the process of inflammation and wound healing to improve treatment and deliver better care for patients.