title: Functional comparison of innate immune signaling pathways in primates.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America. lbarreir@bsd.uchicago.edu
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
authors.forename: John C
authors.initials: JC
authors.lastname: Marioni
authors.forename: Ran
authors.initials: R
authors.lastname: Blekhman
authors.forename: Matthew
authors.initials: M
authors.lastname: Stephens
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011323:Primates / Q000276:immunology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D051193:Toll-Like Receptors