We know of a large number of diseases or medical conditions that affect humans more severely than non-human primates. Humans are more sensitive than chimpanzees to the severe effects of certain virus infections, such as progression of HIV to AIDS or severe complications from hepatitis B. These differences likely arise from different immune responses to infection among species. However, due to the lack of comparative functional data across species, it remains unclear how the immune system of humans and other primates differ.
This paper present the first genome-wide characterization of functional differences in innate immune responses between humans and our closest evolutionary relatives. The results indicate that “core” immune responses, those that are critical to fight any invading pathogen, are the most conserved across primates and that much of the divergence in immune responses is observed in genes that are involved in response to specific microbial and viral agents. Human-specific immune responses are enriched for genes involved in apoptosis and cancer biology, as well as with genes previously associated with susceptibility to infectious diseases or immune-related disorders. Finally, it shows that chimpanzee-specific immune signaling pathways are enriched for HIV–interacting genes. These observations may help explain known inter-species differences in susceptibility to infectious diseases. Though detailed species-specific gene expression patterns were identified in this study, more experiments will be required to assess the phenotypic impact of those unique immune responses. Future studies will also test the immune response of each species to specific infectious agents. This is only the first step in characterizing inter-species differences in immune response.
Functional Comparison of Innate Immune Signaling Pathways in Primates. (2010) PLoS Genet 6(12): e1001249. doi:10.1371/journal.pgen.1001249
Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host–virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV–interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.