@article {311944,
	title = {Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations},
	journal = {Cell},
	volume = {167},
	year = {2016},
	note = {<p>doi: 10.1016/j.cell.2016.09.024</p>
},
	month = {10/2016},
	pages = {643 - 656.e17},
	abstract = {<p>Humans differ in the outcome that follows exposure\&nbsp;to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli?ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus?and mapped expression quantitative trait loci (eQTLs). We identify numerous cis-eQTLs that contribute to the marked differences in immune responses detected within and between populations and a strong trans-eQTL hotspot at TLR1 that decreases expression of pro-inflammatory genes in Europeans only. We find that immune-responsive regulatory variants are enriched in population-specific signals of natural selection and show that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges. Together, our study uncovers evolutionarily important determinants of differences in host immune responsiveness between human populations.Humans differ in the outcome that follows exposure\&nbsp;to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli?ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus?and mapped expression quantitative trait loci (eQTLs). We identify numerous cis-eQTLs that contribute to the marked differences in immune responses detected within and between populations and a strong trans-eQTL hotspot at TLR1 that decreases expression of pro-inflammatory genes in Europeans only. We find that immune-responsive regulatory variants are enriched in population-specific signals of natural selection and show that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges. Together, our study uncovers evolutionarily important determinants of differences in host immune responsiveness between human populations.</p>
},
	isbn = {0092-8674},
	doi = {http://dx.doi.org/10.1016/j.cell.2016.09.024},
	url = {http://www.cell.com/cell/fulltext/S0092-8674(16)31306-X},
	author = {Quach, H{\'e}l{\`e}ne and Rotival, Maxime and Pothlichet, Julien and Loh, Yong-Hwee~Eddie and Dannemann, Michael and Zidane, Nora and Laval, Guillaume and Patin, Etienne and Harmant, Christine and Lopez, Marie and Deschamps, Matthieu and Naffakh, Nadia and Duffy, Darragh and Coen, Anja and Leroux-Roels, Geert and Cl{\'e}ment, Frederic and Boland, Anne and Deleuze, Jean-Fran{\c c}ois and Kelso, Janet and Albert, Matthew~L. and Quintana-Murci, Lluis}
}
