Uncovering the biomedical and evolutionary importance of primate innate immunity

Primates such as chimpanzees differ in the diseases that affect them - especially when we compare them to those that affect us. Progression to AIDs, cancer incidence, Alzheimers disease and malaria either do not affect or cause less severe diseases in non-human primates than they do in humans. So why are our primate cousins so differently affected by these particular diseases than we are? What causes these differences? Are they environmentally mediated? Behavioural? Molecular?

What does the innate immune system have to say about it?

The pathogenesis of disease is an important area of research when trying to understand the origins and progression of diseases. It depends on many variables - host specific, environmental or pathogen specific. A recent publication has sought to understand these differences from the point of view of host factors mainly the innate immune system. By comparing genome-wide gene expression patterns in primary immune cells (monocytes) cultured in vitro from groups of humans, chimpanzees and rhesus macaques and applying bioinformatic analysis to the results, the investigators were able to detect those genes whose expression is altered upon stimulation with lipopolysacharide (LPS), an important activator of the innate immune system. From this data set they could ask, functionally, what makes the human immune system different?



3,170 genes were seen to be differentially expressed with 793 changing in all three species indicating a conserved function. Other genes showed species-specific changes allowing researchers to ask what makes each species unique? More importantly what makes non-human primates different when it comes to diseases? There were 335 genes in the human monocytes that were expressed differently and these were divided between particular pathways.

What does this data have to say about specific diseases?

Those genes listed as being involved in viral infection were those most likely to be species-specific indicating the rapid adaptation of host immunity to fast-evolving viral pathogens. The data sheds light on the possible lo incidence of cancer in non-human primates by detecting the difference in apoptosis/cancer related genes - although the signifigance of monocyte gene expression when considering the whole-organism in diseases such as cancer is difficult to say. Most interestingly seen are those genes involved in HIV infection and AIDs  whose expression may explain why chimpanzees do not progress to AIDs or do so slowly.

Despite the problems in culturing non-human primate immune cells in vitro and the difficulties in controlling for environmental effects (different diets of primates), this study goes some way to understanding at a functional level what makes humans human from an immunological point of view. Although focussing on a single cell type, the monocyte, other cells may prove useful in investigating innate differences - as other cells also function in innate immunity - mucosal epithelium for one. This work paves the way for more detailed molecular analysis but also of more genome-wide work looking at other cells, other activators and pathogens (not LPS but HIV?). Understanding what makes humans different in a pathogenic light should focus not just on immunology at the gene expression level but also differences in epigenomics, behaviour, anatomy and cell biology.

 

 

Varki, Aijit. 2000. A Chimpanzee Genome Project is a Biomedical Imperitive. Genome Res. 2000. 10: 1065-1070. doi: 10.1101/gr.10.8.1065

Barreiro, Luis B., John C. Marioni, Ran Blekhman, Matthew Stephens, and Yoav Gilad. 2010. Functional Comparison of Innate Immune Signaling Pathways in Primates. Ed. Greg Gibson PLoS Genetics 6, no. 12 (December): e1001249. doi:10.1371/journal.pgen.1001249. http://dx.plos.org/10.1371/journal.pgen.1001249.