Luis Barreiro

Research Summary
Our lab aims to understand how natural selection has contributed to the evolution of our species and to which extent past selection events impact present-day susceptibility to disease. Specifically, our group studies the genetic basis of differences in immune response among different individuals and human populations as well as the phenotypic evolution of immune responses in primates. Most projects in the lab are multidisciplinary and combine the use of cutting edge genomic techniques with immunological and evolutionary genetic tools.
Functional Genomics, Population Genetics, Natural Selection, Innate Immunity, Population Variation
  • Lusófona University, Lisbon, Master Biotechnological Engineering 03/2003
  • University of Paris VII, Paris, PhD Population Genetics 03/2008
  • University of Chicago, Chicago, Post-doc Functional Genomics 02/2011
Biosciences Graduate Program Association
  1. Human alveolar macrophage metabolism is compromised during Mycobacterium tuberculosis infection. Front Immunol. 2022; 13:1044592. View in: PubMed

  2. GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology. Immunity. 2023 01 10; 56(1):43-57.e10. View in: PubMed

  3. Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE. Nature. 2023 02; 614(7948):530-538. View in: PubMed

  4. Evolution of immune genes is associated with the Black Death. Nature. 2022 Nov; 611(7935):312-319. View in: PubMed

  5. Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation. J Allergy Clin Immunol. 2023 01; 151(1):260-271. View in: PubMed

  6. Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against influenza virus. Cell Rep. 2022 06 21; 39(12):110974. View in: PubMed

  7. Synchrony and idiosyncrasy in the gut microbiome of wild baboons. Nat Ecol Evol. 2022 07; 6(7):955-964. View in: PubMed

  8. High molecular weight DNA extraction strategies for long-read sequencing of complex metagenomes. Mol Ecol Resour. 2022 Jul; 22(5):1786-1802. View in: PubMed

  9. Lack of evidence for intergenerational inheritance of immune resistance to infections. Nat Immunol. 2022 02; 23(2):203-207. View in: PubMed

  10. Agonism and grooming behaviour explain social status effects on physiology and gene regulation in rhesus macaques. Philos Trans R Soc Lond B Biol Sci. 2022 02 28; 377(1845):20210132. View in: PubMed

  11. Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T?cells influence effector potential. Cell Rep. 2021 11 30; 37(9):110064. View in: PubMed

  12. Genetic ancestry effects on the response to viral infection are pervasive but cell type specific. Science. 2021 Nov 26; 374(6571):1127-1133. View in: PubMed

  13. A signature of Neanderthal introgression on molecular mechanisms of environmental responses. PLoS Genet. 2021 09; 17(9):e1009493. View in: PubMed

  14. Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis. J Clin Invest. 2021 11 15; 131(22). View in: PubMed

  15. A multilayered immune system through the lens of unconventional T cells. Nature. 2021 07; 595(7868):501-510. View in: PubMed

  16. Lung Epithelial Signaling Mediates Early Vaccine-Induced CD4+ T Cell Activation and Mycobacterium tuberculosis Control. mBio. 2021 08 31; 12(4):e0146821. View in: PubMed

  17. Gut microbiome heritability is nearly universal but environmentally contingent. Science. 2021 07 09; 373(6551):181-186. View in: PubMed

  18. Author Correction: Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nat Immunol. 2021 Jul; 22(7):928. View in: PubMed

  19. Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity. Proc Natl Acad Sci U S A. 2021 03 30; 118(13). View in: PubMed

  20. My Old World chap, this a-gal is not for you. Cell Host Microbe. 2021 03 10; 29(3):315-317. View in: PubMed

  21. Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nat Immunol. 2021 01; 22(1):2-6. View in: PubMed

  22. M.?tuberculosis Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity. Cell. 2020 10 29; 183(3):752-770.e22. View in: PubMed

  23. Herd Immunity: Understanding COVID-19. Immunity. 2020 05 19; 52(5):737-741. View in: PubMed

  24. Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity. Nat Commun. 2020 05 11; 11(1):2354. View in: PubMed

  25. Evolutionary and population (epi)genetics of immunity to infection. Hum Genet. 2020 Jun; 139(6-7):723-732. View in: PubMed

  26. The epigenetically-encoded memory of the innate immune system. Curr Opin Immunol. 2020 08; 65:7-13. View in: PubMed

  27. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 06; 20(6):375-388. View in: PubMed

  28. Transposable elements have contributed human regulatory regions that are activated upon bacterial infection. Philos Trans R Soc Lond B Biol Sci. 2020 03 30; 375(1795):20190332. View in: PubMed

  29. IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease. Nature. 2020 02; 578(7796):600-604. View in: PubMed

  30. Efficient and Robust NK-Cell Transduction With Baboon Envelope Pseudotyped Lentivector. Front Immunol. 2019; 10:2873. View in: PubMed

  31. Identification of a ?c Receptor Antagonist That Prevents Reprogramming of Human Tissue-resident Cytotoxic T Cells by IL15 and IL21. Gastroenterology. 2020 02; 158(3):625-637.e13. View in: PubMed

  32. Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques. Proc Natl Acad Sci U S A. 2020 09 22; 117(38):23317-23322. View in: PubMed

  33. Genomic Evidence for Local Adaptation of Hunter-Gatherers to the African Rainforest. Curr Biol. 2019 09 09; 29(17):2926-2935.e4. View in: PubMed

  34. Natural selection contributed to immunological differences between hunter-gatherers and agriculturalists. Nat Ecol Evol. 2019 08; 3(8):1253-1264. View in: PubMed

  35. A Short-Term High-Fat Diet Alters Glutathione Levels and IL-6 Gene Expression in Oxidative Skeletal Muscles of Young Rats. Front Physiol. 2019; 10:372. View in: PubMed

  36. Social affiliation predicts mitochondrial DNA copy number in female rhesus macaques. Biol Lett. 2019 01 31; 15(1):20180643. View in: PubMed

  37. Gene activation precedes DNA demethylation in response to infection in human dendritic cells. Proc Natl Acad Sci U S A. 2019 04 02; 116(14):6938-6943. View in: PubMed

  38. Molecular Signature of CAID Syndrome: Noncanonical Roles of SGO1 in Regulation of TGF-? Signaling and Epigenomics. Cell Mol Gastroenterol Hepatol. 2019; 7(2):411-431. View in: PubMed

  39. Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease. Cell. 2019 02 21; 176(5):967-981.e19. View in: PubMed

  40. Genome-wide quantification of the effects of DNA methylation on human gene regulation. Elife. 2018 12 21; 7. View in: PubMed

  41. Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques. Proc Natl Acad Sci U S A. 2019 01 22; 116(4):1219-1228. View in: PubMed

  42. Polygenic adaptation and convergent evolution on growth and cardiac genetic pathways in African and Asian rainforest hunter-gatherers. Proc Natl Acad Sci U S A. 2018 11 27; 115(48):E11256-E11263. View in: PubMed

  43. Genetic and evolutionary determinants of human population variation in immune responses. Curr Opin Genet Dev. 2018 12; 53:28-35. View in: PubMed

  44. Holy Immune Tolerance, Batman! Immunity. 2018 06 19; 48(6):1074-1076. View in: PubMed

  45. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature. 2018 05; 557(7706):580-584. View in: PubMed

  46. The demographic history and mutational load of African hunter-gatherers and farmers. Nat Ecol Evol. 2018 04; 2(4):721-730. View in: PubMed

  47. BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis. Cell. 2018 01 11; 172(1-2):176-190.e19. View in: PubMed

  48. The contribution of admixture to primate evolution. Curr Opin Genet Dev. 2017 Dec; 47:61-68. View in: PubMed

  49. a7 nicotinic acetylcholine receptor signaling modulates the inflammatory phenotype of fetal brain microglia: first evidence of interference by iron homeostasis. Sci Rep. 2017 09 06; 7(1):10645. View in: PubMed

  50. Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations. Nat Commun. 2017 08 16; 8(1):266. View in: PubMed

  51. Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation. PLoS Genet. 2017 Aug; 13(8):e1006952. View in: PubMed

  52. Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells. Sci Rep. 2017 07 18; 7(1):5702. View in: PubMed

  53. Dispersals and genetic adaptation of Bantu-speaking populations in Africa and North America. Science. 2017 05 05; 356(6337):543-546. View in: PubMed

  54. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science. 2017 04 07; 356(6333):44-50. View in: PubMed

  55. Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans. Genome Biol. 2016 11 29; 17(1):246. View in: PubMed

  56. Social status alters immune regulation and response to infection in macaques. Science. 2016 11 25; 354(6315):1041-1045. View in: PubMed

  57. RNAseq profiling of primary microglia and astrocyte cultures in near-term ovine fetus: A glial in vivo-in vitro multi-hit paradigm in large mammalian brain. J Neurosci Methods. 2017 01 30; 276:23-32. View in: PubMed

  58. Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens. Cell. 2016 Oct 20; 167(3):657-669.e21. View in: PubMed

  59. Genetic and transcriptional analysis of human host response to healthy gut microbiota. mSystems. 2016 Jul-Aug; 1(4). View in: PubMed

  60. Widespread Shortening of 3' Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection. PLoS Genet. 2016 Sep; 12(9):e1006338. View in: PubMed

  61. Dominance rank causally affects personality and glucocorticoid regulation in female rhesus macaques. Psychoneuroendocrinology. 2016 12; 74:179-188. View in: PubMed

  62. Alu repeats as transcriptional regulatory platforms in macrophage responses to M. tuberculosis infection. Nucleic Acids Res. 2016 12 15; 44(22):10571-10587. View in: PubMed

  63. Common methods for fecal sample storage in field studies yield consistent signatures of individual identity in microbiome sequencing data. Sci Rep. 2016 08 16; 6:31519. View in: PubMed

  64. The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation. J Exp Med. 2016 Apr 04; 213(4):585-603. View in: PubMed

  65. Social status drives social relationships in groups of unrelated female rhesus macaques. Anim Behav. 2016 Jan 01; 111:307-317. View in: PubMed

  66. The epigenomic landscape of African rainforest hunter-gatherers and farmers. Nat Commun. 2015 Nov 30; 6:10047. View in: PubMed

  67. Mycobacterial infection induces a specific human innate immune response. Sci Rep. 2015 Nov 20; 5:16882. View in: PubMed

  68. Genome-Wide Association Studies of the Human Gut Microbiota. PLoS One. 2015; 10(11):e0140301. View in: PubMed

  69. Bacterial infection remodels the DNA methylation landscape of human dendritic cells. Genome Res. 2015 Dec; 25(12):1801-11. View in: PubMed

  70. Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution. BMC Genomics. 2015 Sep 03; 16:672. View in: PubMed

  71. Fetal microglial phenotype in vitro carries memory of prior in vivo exposure to inflammation. Front Cell Neurosci. 2015; 9:294. View in: PubMed

  72. bacterial infection drives the expression dynamics of microRNAs and their isomiRs. PLoS Genet. 2015 Mar; 11(3):e1005064. View in: PubMed

  73. Social networks predict gut microbiome composition in wild baboons. Elife. 2015 Mar 16; 4. View in: PubMed

  74. Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium tuberculosis infection. J Clin Invest. 2015 Feb; 125(2):752-68. View in: PubMed

  75. Reservoir host immune responses to emerging zoonotic viruses. Cell. 2015 Jan 15; 160(1-2):20-35. View in: PubMed

  76. The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease. Curr Opin Immunol. 2014 Dec; 31:66-78. View in: PubMed

  77. Editorial Overview: immunogenetics and transplantation: bringing evolution and genomics to human immunology. Curr Opin Immunol. 2014 Oct; 30:v-vii. View in: PubMed

  78. Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers. Proc Natl Acad Sci U S A. 2014 09 02; 111(35):E3596-603. View in: PubMed

  79. When genetics meets epigenetics: deciphering the mechanisms controlling inter-individual variation in immune responses to infection. Curr Opin Immunol. 2014 Aug; 29:119-26. View in: PubMed

  80. Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12. J Immunol. 2014 Jul 15; 193(2):610-6. View in: PubMed

  81. Quantitative trait loci (QTL) study identifies novel genomic regions associated to Chiari-like malformation in Griffon Bruxellois dogs. PLoS One. 2014; 9(4):e89816. View in: PubMed

  82. Exploring the occurrence of classic selective sweeps in humans using whole-genome sequencing data sets. Mol Biol Evol. 2014 Jul; 31(7):1850-68. View in: PubMed

  83. Seasonal variation in human gut microbiome composition. PLoS One. 2014; 9(3):e90731. View in: PubMed

  84. Extracellular adenosine triphosphate affects the response of human macrophages infected with Mycobacterium tuberculosis. J Infect Dis. 2014 Sep 01; 210(5):824-33. View in: PubMed

  85. The impact of agricultural emergence on the genetic history of African rainforest hunter-gatherers and agriculturalists. Nat Commun. 2014; 5:3163. View in: PubMed

  86. A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection. Genome Res. 2014 May; 24(5):850-9. View in: PubMed

  87. Gene set signature of reversal reaction type I in leprosy patients. PLoS Genet. 2013; 9(7):e1003624. View in: PubMed

  88. Different selective pressures shape the evolution of Toll-like receptors in human and African great ape populations. Hum Mol Genet. 2013 Dec 01; 22(23):4829-40. View in: PubMed

  89. Age-dependent association between pulmonary tuberculosis and common TOX variants in the 8q12-13 linkage region. Am J Hum Genet. 2013 Mar 07; 92(3):407-14. View in: PubMed

  90. Getting under?and through?the skin: ecological genomics of chytridiomycosis infection in frogs. Mol Ecol. 2012 Jul; 21(13):3095-7. View in: PubMed

  91. Proteomic characterization of phagosomal membrane microdomains during phagolysosome biogenesis and evolution. Mol Cell Proteomics. 2012 Nov; 11(11):1365-77. View in: PubMed

  92. Social environment is associated with gene regulatory variation in the rhesus macaque immune system. Proc Natl Acad Sci U S A. 2012 Apr 24; 109(17):6490-5. View in: PubMed

  93. Deciphering the genetic architecture of variation in the immune response to Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 2012 Jan 24; 109(4):1204-9. View in: PubMed

  94. Evolutionary genetic dissection of human interferons. J Exp Med. 2011 Dec 19; 208(13):2747-59. View in: PubMed

  95. Don't move: LRRK2 arrests NFAT in the cytoplasm. Nat Immunol. 2011 Oct 19; 12(11):1029-30. View in: PubMed

  96. Evolution of the TIR domain-containing adaptors in humans: swinging between constraint and adaptation. Mol Biol Evol. 2011 Nov; 28(11):3087-97. View in: PubMed

  97. Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family. Hum Mutat. 2011 Jun; 32(6):643-52. View in: PubMed

  98. Evolutionary genetics evidence of an essential, nonredundant role of the IFN-? pathway in protective immunity. Hum Mutat. 2011 Jun; 32(6):633-42. View in: PubMed

  99. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu Rev Immunol. 2011; 29:493-525. View in: PubMed

  100. Functional comparison of innate immune signaling pathways in primates. PLoS Genet. 2010 Dec 16; 6(12):e1001249. View in: PubMed

  101. The role played by natural selection on Mendelian traits in humans. Ann N Y Acad Sci. 2010 Dec; 1214:1-17. View in: PubMed

  102. Formulating a historical and demographic model of recent human evolution based on resequencing data from noncoding regions. PLoS One. 2010 Apr 22; 5(4):e10284. View in: PubMed

  103. From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet. 2010 Jan; 11(1):17-30. View in: PubMed

  104. High-throughput SNP genotyping: combining tag SNPs and molecular beacons. Methods Mol Biol. 2009; 578:255-76. View in: PubMed

  105. Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts. PLoS One. 2009 Aug 06; 4(8):e6540. View in: PubMed

  106. Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet. 2009 Jul; 5(7):e1000562. View in: PubMed

  107. Inferring the demographic history of African farmers and pygmy hunter-gatherers using a multilocus resequencing data set. PLoS Genet. 2009 Apr; 5(4):e1000448. View in: PubMed

  108. Signatures of purifying and local positive selection in human miRNAs. Am J Hum Genet. 2009 Mar; 84(3):316-27. View in: PubMed

  109. Protective role of DC-SIGN (CD209) neck-region alleles with PubMed

  110. Molecular identification of two genotypes of mumps virus causing two regional outbreaks in Asturias, Spain. J Clin Virol. 2008 Aug; 42(4):425-8. View in: PubMed

  111. Natural selection has driven population differentiation in modern humans. Nat Genet. 2008 Mar; 40(3):340-5. View in: PubMed

  112. Promoter and neck region length variation of DC-SIGN is not associated with susceptibility to tuberculosis in Tunisian patients. Hum Immunol. 2007 Nov; 68(11):908-12. View in: PubMed

  113. GHRH proliferative action on somatotrophs is cell-type specific and dependent on Pit-1/GHF-1 expression. J Cell Physiol. 2008 Apr; 215(1):140-50. View in: PubMed

  114. TLR3 deficiency in patients with herpes simplex encephalitis. Science. 2007 Sep 14; 317(5844):1522-7. View in: PubMed

  115. Length variation of DC-SIGN and L-SIGN neck-region has no impact on tuberculosis susceptibility. Hum Immunol. 2007 Feb; 68(2):106-12. View in: PubMed

  116. Signature-tagged transposon mutagenesis identifies novel Mycobacterium tuberculosis genes involved in the parasitism of human macrophages. Infect Immun. 2007 Jan; 75(1):504-7. View in: PubMed

  117. DC-SIGNR neck-region polymorphisms and HIV-1 susceptibility: From population stratification to a possible advantage of the 7/5 heterozygous genotype. J Infect Dis. 2006 Oct 15; 194(8):1184-5; author reply 1185-7. View in: PubMed

  118. Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles. Hum Mol Genet. 2006 Sep 01; 15(17):2650-8. View in: PubMed

  119. DC-SIGN interacts with Mycobacterium leprae but sequence variation in this lectin is not associated with leprosy in the Pakistani population. Hum Immunol. 2006 Jan-Feb; 67(1-2):102-7. View in: PubMed

  120. Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes. Am J Hum Genet. 2006 Mar; 78(3):423-36. View in: PubMed

  121. Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. PLoS Med. 2006 Feb; 3(2):e20. View in: PubMed

  122. The heritage of pathogen pressures and ancient demography in the human innate-immunity CD209/CD209L region. Am J Hum Genet. 2005 Nov; 77(5):869-86. View in: PubMed