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Gene Expression Study Offers Clues About Primate Immune Differences

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – In a paper appearing online last night in PLoS Genetics, University of Chicago researchers used gene expression profiling to track down some of the immune differences that exist between three primate species: humans, chimps, and rhesus macaques.

The team profiled and compared gene expression patterns in white blood cells from each of the three primate species that were responding to an immune challenge. Although their results suggest genes involved in general immune responses share similar patterns in all three primates, the researchers also uncovered species-specific patterns — particularly with respect to genes known to contribute to immune responses to viral or bacterial infection.

"Our results indicate that 'core' immune responses, those that are critical to fight any invading pathogen, are the most conserved across primates," senior author Yoav Gilad, a human genetics researcher at the University of Chicago, and co-authors wrote, "and that much of the divergence in immune responses is observed in genes that are involved in response to specific microbial and viral agents."

Although closely related primate species seem to share many of the same immune system components, they explained, different primate species often respond differently to similar immune challenges. For instance, they noted, humans frequently fare worse than non-human primates when it comes to fighting immune challenges that range from viral infections to cancer and Alzheimer's disease.

"Differences in susceptibility to infectious agents between humans and other primates might be explained, at least in part, by inter-species differences in immune response to infection," they wrote. "Indeed, a large body of work indicates that immune systems are rapidly evolving."

In an effort to learn more about the features that underlie such differences in primate immunity, particularly within the innate branch of the immune system, Gilad and co-workers used multi-species microarrays to look at the expression of roughly 18,100 genes in human, chimpanzee, and rhesus macaque monocytes.

The white blood cells had been stimulated with lipopolysaccharide for between four and 24 hours, they explained — a treatment intended to kick start inflammatory immune responses as well as some of the pathways that become activated during bacterial or viral infections.

The team detected 3,170 genes showing altered expression in primate cells following LPS treatment.

Of these, 793 genes showed similar expression changes in all three species. Among them were genes known to contribute to inflammation in general, along with genes from several transcription factor, immune receptor, and signaling pathways — including TLR4 and other genes in the Toll-like receptor pathway.

Such TLRs can trigger both general and more specialized signals in response to infection, the authors explained, and help cells in the immune system recognize and destroy foreign invaders.

These and other shared expression clues indicate that "monocytes from all three species responded to the treatment with LPS by engaging TLP4-mediated regulatory pathways, leading to the induction of pro-inflammatory and anti-viral immune responses via the activation of [the transcription factor NF-kappaB] and [interferon regulatory factor] mediated pathways," the researchers argued.

Overall, they noted, some 58 percent of general infection-response genes tested had comparable expression patterns after LPS treatment in cells from all of the primates.

In contrast, though, when the team narrowed in on genes that are thought to be involved in more specific responses to viruses or bacteria, they found that fewer than a third of the genes tested had similar expression patterns in the three primates.

Rather, genes from immune pathways responding to bacterial and viral infection — as well as apoptosis-related genes — tended to have more diverse expression patterns when the researchers compared the three primates.

"We found that the universal TLR response is remarkably more conserved across primates compared to microbial-specific responses," the researchers wrote, explaining that such patterns may reflect the fact that the more general immune pathways are under stronger evolutionary constraints than those contributing to relatively specialized immune responses.

For instance, they found that certain genes that code for HIV-interacting proteins are particularly highly expressed in LPS treated chimpanzee monocytes — consistent with the notion that chimp immune systems may be better prepared to combat HIV infection than human immune systems.

Though they emphasized that much more research is needed to more fully compare immune patterns in primates, those involved in the study say it's a "first step in characterizing inter-species differences in immune response."

"We expect future comparative studies in primates to focus on the immune response to different individual infectious agents," they concluded.

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