APOL3 & Its New Insight into Cell-Autonomous Immunity: An Overview
By Tanvi Peddireddi
Using CRISPR gene editing, researchers have found APOL3, a protein that protects the human epithelium, endothelium, and fibroblasts from infection
APOL3 uses detergent-like powers to dissolve bacterial membranes
APOL3 can provide cell-autonomous immunity to our bodies
Nonimmune cells, such as epithelial cells, mesenchymal cells, and stromal cells, are important fighters to fend off diseases when the immune cells cannot. These cells are often overlooked, but they have been part of a prehistoric defense system. The credit can be given to the apolipoprotein named APOL3. Many scientists and researchers regard this protein as "soap-like" due to its capacity to adhere to bacterial lipid membranes and dissolve chunks of the wall into the intracellular fluid. Recent findings have shown that APOL3 isn’t only limited to the immune system, however. Because it is present throughout the body, this tiny protein can provide wide protection.
What does the data show?
John MacMicking's research on APOL3 provides new insight into cell-autonomous immunity, the process by which our body can defend itself. In their study, his team infected nonimmune cells with Salmonella, a rod-shaped bacteria responsible for food poisoning and affecting the intestines, and monitored the way the cells responded to the bacterial invasion. The team found that the immune cytokine interferon-γ (IFN-γ) was able to control life-threatening infections in the human body, but they weren’t sure which protein they could give credit to for destroying these bacteria. After MacMicking’s team analyzed over 19,000 human cell genes for those that potentially encode protective proteins, the research team discovered that APOL3 was able to break through the bacterium’s inner membrane with the help of GBP1 damaging the outer membrane. The protein's "soap-like" property was proved by APOL3 possessing regions that can attract water and lipids. By eliminating the lipid chunks, it was possible to tear down the inner membrane. The discovery of this detergent-like protein can prove to help fight infections and support the immune system overall.
What does this mean for us?
Although researchers are far from applying this discovery to therapies for infections, this protein can prove to be one of many ways of defending the body from microbes that are becoming resistant to traditional antibiotics. With APOL3 there to protect the body, modern healthcare will be able to rely on their abilities to treat many illnesses, from organ transplants to even cancer therapy. The immune system has already established strategies for eliminating harmful cells, and APOL3 is only another mechanism among many. With the help of these mechanisms, medical costs will lower significantly, reduce the use of intensive treatments, and, in time, increase mortality rates across all parts of the world. Even though APOL3 is just one protein out of the tens of thousands of proteins in the human body, this discovery can unpack many new and improved tools to fight infections.