Immune resilience: The key to a long and healthy life

Defying inflammation: How immune resilience enhances longevity and infection immunity.


The concept of “immune resilience” has emerged as a crucial factor in promoting longevity and resistance to infections in individuals. Immune resilience refers to the ability of the immune system to effectively adapt and respond to various challenges, stresses, and threats posed by pathogens, environmental factors, and internal imbalances.

In a recent discovery, researchers at The University of Texas Health Science Center in San Antonio and teams in five other countries discovered that some people can better resist infections and stress that causes inflammation. 

They call this ability “immune resilience.” They came up with a particular way to measure how strong someone’s immune resilience is. This can help doctors make better healthcare choices and let researchers understand why some people live longer and stay healthier, even if they’re the same age. Their research results were published in a journal called Nature Communications.

To do this research, they got support from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. They also received help from the U.S. Veterans Health Administration and the Doris Duke Charitable Foundation.

Even though age usually affects how our bodies respond to infections and inflammation, some people can keep their immune systems strong no matter how old. Sunil K. Ahuja, a professor at UT Health Science Center in San Antonio who specializes in infectious diseases, explained this. He said, “some individuals can maintain a sound immune system and reduce inflammation even when their body is stressed.”

Weijing He, another researcher, added that immune resilience means having a strong immune system and less inflammation even when the body is dealing with stress. They discovered that as people age and face inflammation, some folks can still keep their immune resilience from weakening.

Researchers created tests to check how strong people’s immune systems are. They tested these on almost 50,000 individuals of different ages with different immune challenges. They found that those with the most vital immune systems were more likely to:

  1. Live longer.
  2. Be able to fight off HIV and the flu.
  3. Resist AIDS.
  4. Not have their skin cancer come back after a kidney transplant.
  5. Survive COVID-19.
  6. Survive sepsis (a severe infection).

The researchers used two methods to measure immune resilience:

  1. They checked the balance between two white blood cell types, CD8+ and CD4+ T-cells. These cells fight infections, but their balance can be off in many diseases. They divided the balance into four groups and checked it in people with various disorders and of different ages.
  2. They looked at the levels of specific genes linked to robust immune systems and better chances of survival. They also looked at genes linked to more inflammation and a higher risk of death. They found that the genes that showed strong immune systems and low inflammation matched the best immune resilience.

Co-author Grace C. Lee, PharmD, PhD, research investigator at the VA Center for Personalized Medicine and assistant professor at The University of Texas at Austin College of Pharmacy, explained, “Many people think of inflammation alone when considering disease outcomes. However, immune resilience captures levels of immunocompetence and inflammation together.”

“This study brings a new idea called immune resilience, which focuses on the balance between having a strong immune system and having inflammation. This balance is important for staying healthy, no matter how old you are. It’s a step forward because it helps us see more than just inflammation. We might find new ways to prevent and treat diseases like heart problems, COVID-19, HIV/AIDS, and cancers,” said Lee, one of the researchers.

Understanding the Framingham Study

Muthu Saravanan Manoharan, another researcher, explained that they divided people from the Framingham Heart Study into four groups based on their immune resilience genes. “People who had the best immune resilience, shown by genes that meant strong immune systems and low inflammation, lived longer even when we considered their age and gender. Those with genes that meant weak immune systems and high inflammation died sooner. People with genes showing either strong immune systems and high inflammation or weak immune systems and low inflammation lived in between,” Manoharan explained.

Flu Insights

The researchers looked at how genes react during the flu. They studied healthy college students and people under 50 from the community who had their blood taken before flu season. When they got the flu, most had genes showing weaker immune systems and more inflammation, often seen in shorter lifespans. Even those with robust immune systems couldn’t fully recover after getting sick. “Even six months after the flu, some people still had signs of a weak immune system,” explained Nathan Harper, one of the researchers. “This is interesting because it means the flu and similar illnesses can weaken the immune system for a long time.”

Learning from Sex Workers

The study also looked at women who worked as sex workers in Kenya. During a lengthy research, they found that those who had unprotected sex often had weaker immune systems. “Most of the women who got HIV had weaker immune systems,” explained Lyle R. McKinnon, another researcher.

HIV-AIDS Connections

In one group of people, the researchers found something rare. Some people can keep their immune systems strong even when they have HIV. This virus usually weakens the immune system. “Surprisingly, we found that some young adults still had strong immune systems even with HIV,” said Jason F. Okulicz, a doctor and researcher. “These strong immune systems helped them avoid AIDS and keep the HIV under control. Amazingly, those who started taking medicine for HIV early on showed strong immune systems like young adults without HIV.”

COVID-19 Impact

The researchers also saw a link between robust immune systems and how people reacted to infections like COVID-19. About 80% of people with COVID-19 had weak immune systems, and their immune systems predicted if they would survive, no matter their age. “Even in serious cases like pneumonia and sepsis, people with better immune systems when they got to the hospital were more likely to survive,” added Justin Meunier, another researcher.

People who receive kidney transplants were also studied for immune resilience. These individuals are at a much higher risk of getting skin cancer. Researchers wanted to see if their immune health affected their chances of getting a second cancer. They found that if someone had a strong immune system when they got the first cancer, they were less likely to get a second one.

In collaboration with researchers from Sardinia, the team looked at the blood cells of about 4,000 healthy people. They found that those with weaker immune systems had blood cell profiles that showed their immune system was working too much. It was also observed in nonhuman primates with soft immune resilience.

They noticed that age wasn’t the only thing that determined how someone’s immune system reacted to stress. Some younger people with weak immune systems had the same signs usually seen in older people. The ability to keep a robust immune system when you’re young might be linked to how long you live. Another finding was that more women had strong immune resilience than men in all the groups they studied.

Checking Immune Health

Ahuja mentioned that checking immune health could be significant for public health. By looking at the CD8+ and CD4+ cells, we can see how strong someone’s immune system is. This can help us understand who might get diseases affecting the immune system, how healthy treatments work, and how much someone might recover.

Journal Reference:

  1. Ahuja, S.K., Manoharan, M.S., Lee, G.C. et al. Immune resilience, despite inflammatory stress, promotes longevity and favorable health outcomes, including resistance to infection. Nature Communications. DOI: 10.1038/s41467-023-38238-6.
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