Autonomous cellular immunity shaped human evolution

image: Jessica Brinkworth, anthropology professor, studies the evolution of human immune function and its impact on susceptibility to serious infections.
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Credit: Photo by Fred Zwicky

CHAMPAIGN, Illinois – Each human cell harbors its own defenses against invading microbials, drawing on strategies that date back to some of the earliest events in life history, the researchers report. Because this “autonomous cellular immunity” is so old and persistent, understanding it is essential for understanding human evolution and human medicine, the researchers said.

Like amoeba, most human cells can transform to engulf and degrade foreign agents in a process known as phagocytosis, said Jessica brinkworth, professor of anthropology at the University of Illinois, Urbana-Champaign, who wrote the new report with former undergraduate Alexander Alvarado. And the methods used by human cells to detect, pierce or hack invading microbes are inherited – 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 are going to study humans, you have to accept that immunity will always be part of what you look at. And you have to go deep into the time of evolution.”

The authors reject the idea that the immune system is separate from other bodily systems.

“Immunity is literally everywhere,” Brinkworth said. “The whole organism, from the skin to the level of the last enzyme floating anywhere in the body, almost everything is engaged in some form of protection.”

For this reason, she suggests that medical approaches to infection control that attempt to reduce evolutionary conserved immune responses, such as pro-inflammatory pathways, are flawed. Although it may be useful or necessary to use immunosuppressive drugs against autoimmune diseases or in the case of organ transplants, these drugs do not appear to work against serious microbial infections.

“Against the background of serious infections, there have been many attempts to find ways to reduce the immune response by throwing a bunch of steroids into 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, studied by Brinkworth, this approach was not successful.

“Over 100 trials of immunomodulatory approaches to sepsis have failed,” she said. “And the only drug that came on the market then failed. Most of these drugs have tried to block highly conserved evolutionary defenses, such as the mechanisms of cellular autonomic immunity.”

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

Likewise, anthropologists often fail to consider how millions of years of fighting 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 a physiological system, at some point you’ll have to ask yourself how pathogens shaped it,” she said.

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Brinkworth is also an affiliate of the Carl R. Woese Institute for Genomic Biology at U. of I.

Editor’s Notes:

To reach Jessica Brinkworth, email [email protected]

The article “Cellular immunity and pathogen-mediated human evolution: or how our prokaryotic and unicellular origins affect the history of human evolution” is available online and U. of I. News Bureau


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