Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
PLoS Genet. 2010 Dec 16;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.
人类对大量感染的反应不同于其他灵长类动物。人类与其他灵长类动物对感染原的易感性差异可能是由于对感染的免疫反应存在种间差异。这一观点认为，与免疫相关的过程中涉及的基因在灵长类动物中近期正选择的靶标中强烈富集，这表明免疫反应迅速进化，但仅为可能的种间功能差异提供了间接证据。为了直接比较灵长类动物的免疫反应，我们用脂多糖（LPS）刺激人类、黑猩猩和恒河猴的原代单核细胞，并研究了随后的时间过程调节反应。我们发现，虽然普遍的 Toll 样受体反应在灵长类动物中大多是保守的，但与病毒感染相关的调节反应通常是谱系特异性的，可能反映了快速的宿主-病毒相互适应循环。此外，人类特异性免疫反应富含参与细胞凋亡的基因，以及与癌症以及传染病或免疫相关疾病易感性相关的基因。最后，我们发现，黑猩猩特异性免疫信号通路富含 HIV 相互作用基因。总之，我们的观察结果强烈支持这样一种观点，即谱系特异性免疫反应可能有助于解释已知的对传染病易感性的种间差异。
