functional comparison of innate immune signaling pathways in primates在灵长类动物先天免疫信号通路的功能比较.pdfVIP

Functional Comparison of Innate Immune Signaling Pathways in Primates 1 1 1¤ 1,2 1 Luis B. Barreiro *, John C. Marioni , Ran Blekhman , Matthew Stephens , Yoav Gilad * 1 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America, 2 Department of Statistics, University of Chicago, Chicago, Illinois, United States of America 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