Cell-autonomous immunity shaped human evolution

September 09, 2020

CHAMPAIGN, Ill. -- Every human cell harbors its own defenses against microbial invaders, relying on strategies that date back to some of the earliest events in the history of life, researchers report. Because this "cell-autonomous immunity" is so ancient and persistent, understanding it is essential to understanding human evolution and human medicine, the researchers said.

Like amoebae, most human cells can transform themselves to engulf and degrade foreign agents in a process known as phagocytosis, said Jessica Brinkworth, a professor of anthropology at the University of Illinois, Urbana-Champaign who wrote the new report with former undergraduate student Alexander Alvarado. And the methods that human cells use to detect, pierce or hack up invading microbes are inherited from - and shared by - bacteria and viruses, she said.

"Every cell has these things and they have this deep evolutionary history," Brinkworth said. "This means that if you're going to study humans, you need to accept that immunity is always going to be part of what you're looking at. And you're going to have to go deep into evolutionary time."

The authors reject the notion that the immune system is distinct from other bodily systems.

"Immunity is literally everywhere," Brinkworth said. "The whole of the organism, from the skin down to the level of the last enzyme floating anywhere in the body, almost all of it is engaged in protection in one form or another."

For that reason, she suggests that medical approaches to fighting infection that try to tamp down evolutionarily conserved immune responses such as pro-inflammatory pathways are misguided. While it can be useful or necessary to use immune-suppressing drugs against autoimmune conditions or in the case of organ transplants, such drugs do not appear to work against severe microbial infections.

"In the context of severe infections, there have been many attempts to come up with ways of reducing the immune response by throwing a bunch of steroids at it or blocking the body's ability to detect the pathogen," Brinkworth said. "But targeting these immune mechanisms that have been around for millions of years is potentially counterproductive."

In the case of sepsis, which Brinkworth studies, this approach has not been fruitful.

"More than 100 trials of immunomodulatory approaches to sepsis have failed," she said. "And the one drug that made it to market then failed. Most of these drugs tried to block highly evolutionarily conserved defenses, like mechanisms of cell-autonomous immunity."

Many immunomodulatory drugs now being tested against the new coronavirus are failed sepsis drugs, she said.

Similarly, anthropologists often fail to consider how millions of years of battle against infections at the cellular level have shaped human genetics, physiology and even behavior, Brinkworth said.

"If you're talking about human evolution, if you're in any physiological system, you're going to have to address at some point how pathogens have shaped it," she said.
Brinkworth also is an affiliate of the Carl R. Woese Institute for Genomic Biology at the U. of I.

Editor's notes:

To reach Jessica Brinkworth, email jfbrinkw@illinois.edu.

The paper "Cell-autonomous immunity and the pathogen-mediated evolution of humans: Or how our prokaryotic and single-celled origins affect the human evolutionary story" is available online and from the U. of I. News Bureau

University of Illinois at Urbana-Champaign, News Bureau

Related Sepsis Articles from Brightsurf:

Hormone involved in obesity is a risk factor for sepsis
A group of scientists from Instituto Gulbenkian de Ciência (IGC), led by Luís Moita, discovered that a hormone that has been pointed out as a treatment for obesity reduces the resistance to infection caused by bacteria and is a risk factor for sepsis.

Antihypotensive agent disrupts the immune system in sepsis
Patients who go into shock caused by sepsis (septic shock) are treated with the antihypotensive agent norepinephrine.

Milestone for the early detection of sepsis
Researchers from Graz, Austria, are developing a ground-breaking method that uses biomarkers to detect sepsis 2 to 3 days before the first clinical symptoms appear.

Breast milk may help prevent sepsis in preemies
Researchers at Washington University School of Medicine in St. Louis and Mayo Clinic in Rochester, Minn., have found -- in newborn mice -- that a component of breast milk may help protect premature babies from developing life-threatening sepsis.

Finding a new way to fight late-stage sepsis
Researchers have developed a way to prop up a struggling immune system to enable its fight against sepsis, a deadly condition resulting from the body's extreme reaction to infection.

Study: Sepsis survivors require follow-up support
Survivors of sepsis -- a life-threatening response to an infection -- have expressed a need for advocacy and follow-up support, according to a study authored by professors at the University of Tennessee, Knoxville, and the University of Tennessee Health Science Center in Memphis, and published in Dimensions of Critical Care Nursing.

After decades of little progress, researchers may be catching up to sepsis
After decades of little or no progress, biomedical researchers are finally making some headway at detecting and treating sepsis, a deadly medical complication that sends a surge of pathogenic infection through the body and remains a major public health problem.

Study changes guidelines for sepsis management
University of Arizona Health Sciences researcher ends debate among physicians regarding sepsis management.

Improving outcomes for sepsis patients
More than 1 million sepsis survivors are discharged annually from acute care hospitals in the United States.

Genes linked to death from sepsis ID'd in mice
Bacteria in the bloodstream can trigger an overwhelming immune response that causes sepsis.

Read More: Sepsis News and Sepsis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.