Primate Immune Systems Offer Clues to Combating Disease

Humans may be smarter than our primate cousins, but research has shown their immune systems may trump ours, in some ways. We tend to be more susceptible to HIV, cancer, hepatitis and other infectious diseases than some of our closest relatives.

Because humans share the majority of our genetic makeup with other primates, scientists at the University of Chicago set out to uncover some of the small differences in the innate immune systems of humans, macaque monkeys and chimpanzees – the latter being humans' closest evolutionary relative. Changes that have arisen in our immune systems since we split from a common ancestor might give clues for disease research.

"We believe these differences in susceptibility are probably differences in immune response," said Luis Barreiro, co-author of a study published today (Dec. 16) in the journal Public Library of Science.

Barreiro and his colleagues took blood samples from six macaque monkeys, six people and six chimpanzees. They tested the effects of diseases on each species by adding a chemical made by bacteria to the blood samples, and then observed the gene activity in the blood cells in response.

At first, all three species had the same "core" initial immune response to lipopolysaccharide (LPS), a molecule that's found on the surface of bacteria.

But after kick-starting the immune system, researchers found differing gene activity across the species. In humans, more gene sets were activated that have been linked to cancer biology, cell death and immune disorders. In chimpanzees, researchers saw greater activity in genes related to warding off HIV.

Evolving new immune systems

Macaques and humans branched off from a common ancestor 13 million years ago, Barreiro said. But chimpanzees and humans diverged from a common ancestor much later, about 5 million years ago.

By comparing blood from all three, Barreiro and his colleagues built a picture of which immune responses were originally shared by all, and which evolved along the way within each species. Barreiro said he was pleasantly surprised that the differences between the three species that the experiment revealed correlated with observed differences between the species in the real world.

"There are a few differences in medical traits between human and non-human primates, one is [humans' greater susceptibility to] HIV, a second one is humans tend to develop cancer at a much higher rate than other primates," Barreiro said.

Narrowing down the genes related to these immune response differences may lead to new research targets among people infected with these diseases, he told MyHealthNewsDaily.

Can comparing humans with other primates fight disease?

Dr. Warner C. Greene, director of the Gladstone Institute of Virology and Immunology at the University of California, San Francisco, said researching primates who are resistant to HIV is a known tactic in the fight against AIDS.

Greene said the Sooty Mangabey monkey is a prime example of a monkey that's intrigued HIV researchers.

"When HIV is injected into the Sooty Mangabeys, they develop very high viral loads," Greene said. "But they won't develop AIDS."

By studying the Sooty Mangabey and other primates who have immunity to HIV, Greene said researchers aim to discover how to mimic this immunity in humans.

Yet for all the intriguing connections between gene activity and real-world differences between the species, Greene and Barreiro say the study's findings are preliminary. More research would be needed to start new infectious disease experiments.

Instead of using immunity activators such as LPS, Barreiro said the next step is to " actually infect the cells with different pathogens.

In the meantime, Barreiro's paper has caught the eye of other scientists as a new research approach.

Comparing animal genomes for medical research

"It's a nice piece of work," said Dr. Duncan Odom, a principal investigator at the University of Cambridge Cancer Center in the U.K.

Odom was intrigued by the HIV and cancer implications the study found. But he also noted that the LPS – the chemical used in Barreiro's experiment – is made by bacteria. Using bacteria-like immune system stimulants may not be the best way to get information about the body's reaction to viruses such as HIV or hepatitis.

More importantly than its HIV implications, Odom said, the paper opened up research into the evolution of immune systems.

He also sees the research as symbol of the power of emerging genomic research.

"Traditionally, we thought that a mouse was our model organism," Odom said, explaining that most medical research has been done with mice as a model for humans.

Now, with more animal genomes mapped and experiments such as Barreiro's, Odom said, "We can get a lot of information from species that we normally would not think of as a source of information."

"Five years ago, this would be an impossible study do to, full stop," Odom said. "This is going to become a very increasing theme in the next 20 years."

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