How Does the Body Know When to Stop Fighting Infections

COVID-19 shaped the past year in scientific research, including efforts to understand how the virus infects our cells and how vaccines and treatments can combat it. Researchers have paid particularly close attention to how immune systems react to the novel coronavirus. A healthy and active immune system can effectively fight disease, but one on overdrive can be detrimental. And studies show that in response to SARS-CoV-2 infection, the immune response can actually cause significant harm in certain cases, resulting in death or what is known as long COVID, where symptoms persist indefinitely.

This phenomenon does not occur only with COVID-19. Anytime the immune system fails to stop responding as intended, chronic inflammation and autoimmune reactions can occur, leading some people to suffer long-term symptoms and even organ damage.

Pew-funded scholars and fellows have long sought to better understand how the immune system operates to fight infections and keep us healthy. Although some scientists focus on ways in which the immune system attacks viruses and bacteria, the work highlighted here explores the mechanisms that help people maintain immune system balance. That’s when bodies are primed to combat infections, but also to avoid overreactions that can cause further bodily harm.     

Balancing immune system responses

In a typical immune response, the body experiences temporary inflammation as immune cells work to combat infection. In some cases, however, this inflammation fails to dissipate, which can cause damage to organs and tissues. Using techniques in cell and molecular immunology, tissue microscopy, and mouse genetics, José Ordovás-Montañés, a 2021 Pew biomedical scholar, is investigating how immune responses can deteriorate into chronic inflammation and eventually compromise tissue function.

Ordovás-Montañés’ laboratory is based in Boston Children’s Hospital, where his work looks at the role that nonimmune cells in the skin, airway, and intestinal lining play in the inflammatory response. His team’s findings could help inform strategies to reduce tissue damage during infections.

When a body mounts an immune reaction to fight pathogens, it needs to know when to stop or whether to keep fighting. The body’s ability to turn an immune response off is critical in determining the outcome of an infection, especially in diseases such as COVID-19, where some patients experience life-threatening lung injuries from immune overreactions to the virus.

Luciana Pádua Tavares, a 2020 Pew Latin American fellow based at Brigham and Women’s Hospital in Boston, is examining what happens when uncontrolled immune responses leave individuals susceptible to bacterial infections following bouts with influenza. Using techniques in molecular immunology and genetics, she will assess how the influenza virus can alter the function of immune and lung cells and suppress recovery in mice. This work could help reveal why some infections make certain people more susceptible to pneumonia and lung damage.

Tracking down damaged tissues

The immune system is primarily known for its ability to fight off infections, but immune cells also track down damaged tissues to remove debris and cellular waste. These processes are integral to helping the body heal properly but are less well understood by scientists. Christoph Thaiss is a 2020 Pew scholar based at the University of Pennsylvania. His lab is investigating how immune cells contribute to tissue health by probing the mechanisms that they use to sense tissue damage and the molecules involved in the damage-sensing pathway.

Similarly, 2021 Pew scholar Justin Perry, who leads a lab at the Memorial Sloan-Kettering Cancer Center in New York, is studying the processes that control the ability of macrophages, a type of immune cell, to engulf and redistribute matter from dead cells to avoid triggering a potentially damaging inflammatory response. Both researchers’ work could inform new strategies to enhance tissue tolerance to injury-induced inflammation and help the body recover more quickly from illness.

Immune interactions in the gut

Daria Esterhazy, a 2020 Pew scholar whose lab is at the University of Chicago, is studying how gastrointestinal infections can trigger an immune reaction in the pancreas. In earlier work, she discovered that white blood cells, which are part of the immune system, move from the small intestine to the pancreas through the lymphatic system. In infected intestines, inflammation can spread to the pancreas and trigger autoimmune conditions such as diabetes.

Using techniques in microbiology, immunology, and molecular biology, Esterhazy plans to track the movement of immune cells to the pancreas during infections from bacteria and viruses. Her work could reveal how immune balance is maintained and controlled in the digestive tract and offer new approaches for treating pancreatic disorders such as diabetes, pancreatitis, and even pancreatic cancer.

The immune system is a complex web of organs, cells, and tissues constantly working to protect people from pathogens and prevent bodily injury. Research by scientists studying how the immune system operates and, more importantly, how to maintain immune system balance can provide valuable insight into how bodies can more effectively and efficiently combat infection, as well as recover more quickly. 

Kara Coleman is the director of and Jennifer Villa is an officer with The Pew Charitable Trusts’ biomedical programs, including the biomedical scholars, Pew-Stewart Scholars for Cancer Research, and Latin American fellows programs.