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  1. Article ; Online: Shaping immunity: The influence of natural selection on population immune diversity.

    Randolph, Haley E / Aracena, Katherine A / Lin, Yen-Lung / Mu, Zepeng / Barreiro, Luis B

    Immunological reviews

    2024  

    Abstract: Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population-level susceptibility to infectious diseases and immune disorders. Although the factors ... ...

    Abstract Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population-level susceptibility to infectious diseases and immune disorders. Although the factors influencing immune response diversity are partially understood, what mechanisms lead to the wide range of immune traits in healthy individuals remain largely unexplained. Here, we discuss the role that natural selection has played in driving phenotypic differences in immune responses across populations and present-day susceptibility to immune-related disorders. Further, we touch on future directions in the field of immunogenomics, highlighting the value of expanding this work to human populations globally, the utility of modeling the immune response as a dynamic process, and the importance of considering the potential polygenic nature of natural selection. Identifying loci acted upon by evolution may further pinpoint variants critically involved in disease etiology, and designing studies to capture these effects will enrich our understanding of the genetic contributions to immunity and immune dysregulation.
    Language English
    Publishing date 2024-04-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13329
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  2. Article ; Online: Herd Immunity: Understanding COVID-19.

    Randolph, Haley E / Barreiro, Luis B

    Immunity

    2020  Volume 52, Issue 5, Page(s) 737–741

    Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, has demonstrated the devastating impact of a novel, infectious pathogen on a susceptible population. Here, we explain the basic concepts ... ...

    Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, has demonstrated the devastating impact of a novel, infectious pathogen on a susceptible population. Here, we explain the basic concepts of herd immunity and discuss its implications in the context of COVID-19.
    MeSH term(s) Basic Reproduction Number ; Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Coronavirus Infections/transmission ; Global Health ; Humans ; Immunity, Herd ; Models, Immunological ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Pneumonia, Viral/transmission ; SARS-CoV-2 ; Vaccination ; Vaccination Coverage
    Keywords covid19
    Language English
    Publishing date 2020-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2020.04.012
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  3. Article ; Online: Herd Immunity

    Randolph, Haley E. / Barreiro, Luis B.

    Immunity

    Understanding COVID-19

    2020  Volume 52, Issue 5, Page(s) 737–741

    Keywords Immunology ; Immunology and Allergy ; Infectious Diseases ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2020.04.012
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Holy Immune Tolerance, Batman!

    Randolph, Haley E / Barreiro, Luis B

    Immunity

    2018  Volume 48, Issue 6, Page(s) 1074–1076

    Abstract: Bats are reservoir hosts of numerous viruses that cause severe pathology in humans. How bats cope with such pathogens remains elusive. In a recent issue of Cell, Pavlovich et al. (2018) describe several key adaptations in innate immune-related genes that ...

    Abstract Bats are reservoir hosts of numerous viruses that cause severe pathology in humans. How bats cope with such pathogens remains elusive. In a recent issue of Cell, Pavlovich et al. (2018) describe several key adaptations in innate immune-related genes that suggest that the Egyptian rousette fruit bat relies on immune tolerance mechanisms to manage viral infections.
    MeSH term(s) Animals ; Antiviral Agents ; Chiroptera ; Egypt ; Humans ; Immune Tolerance ; Immunity
    Chemical Substances Antiviral Agents
    Keywords covid19
    Language English
    Publishing date 2018-06-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2018.05.016
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  5. Article: Herd Immunity: Understanding COVID-19

    Randolph, Haley E / Barreiro, Luis B

    Immunity

    Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, has demonstrated the devastating impact of a novel, infectious pathogen on a susceptible population. Here, we explain the basic concepts ... ...

    Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, has demonstrated the devastating impact of a novel, infectious pathogen on a susceptible population. Here, we explain the basic concepts of herd immunity and discuss its implications in the context of COVID-19.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #125391
    Database COVID19

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  6. Article ; Online: Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against influenza virus.

    Downey, Jeffrey / Randolph, Haley E / Pernet, Erwan / Tran, Kim A / Khader, Shabaana A / King, Irah L / Barreiro, Luis B / Divangahi, Maziar

    Cell reports

    2022  Volume 39, Issue 12, Page(s) 110974

    Abstract: Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be ... ...

    Abstract Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be countered by largely uncharacterized disease tolerance mechanisms. Here, we show that mitochondrial cyclophilin D (CypD) protects against IAV via disease tolerance. CypD
    MeSH term(s) Animals ; Peptidyl-Prolyl Isomerase F ; Humans ; Influenza A virus ; Influenza, Human ; Interleukins ; Killer Cells, Natural ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Orthomyxoviridae Infections ; Interleukin-22
    Chemical Substances Peptidyl-Prolyl Isomerase F ; Interleukins
    Language English
    Publishing date 2022-06-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2022.110974
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  7. Article ; Online: Genetic and evolutionary determinants of human population variation in immune responses.

    Sanz, Joaquin / Randolph, Haley E / Barreiro, Luis B

    Current opinion in genetics & development

    2018  Volume 53, Page(s) 28–35

    Abstract: Humans display remarkable immune response variation when exposed to identical immune challenges. However, our understanding of the genetic, evolutionary, and environmental factors that impact this inter-individual and inter-population immune response ... ...

    Abstract Humans display remarkable immune response variation when exposed to identical immune challenges. However, our understanding of the genetic, evolutionary, and environmental factors that impact this inter-individual and inter-population immune response heterogeneity is still in its early days. In this review, we discuss three fundamental questions concerning the recent evolution of the human immune system: the degree to which individuals from different populations vary in their innate immune responses, the genetic variants accounting for such differences, and the evolutionary mechanisms that led to the establishment of these variants in modern human populations. We also discuss how past selective events might have contributed to the uneven distribution of immune-related disorders across populations.
    MeSH term(s) Evolution, Molecular ; Gene-Environment Interaction ; Genetic Heterogeneity ; Genetics, Population ; Humans ; Immunity, Innate/genetics
    Language English
    Publishing date 2018-06-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2018.06.009
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  8. Article ; Online: Genetic ancestry effects on the response to viral infection are pervasive but cell type specific.

    Randolph, Haley E / Fiege, Jessica K / Thielen, Beth K / Mickelson, Clayton K / Shiratori, Mari / Barroso-Batista, João / Langlois, Ryan A / Barreiro, Luis B

    Science (New York, N.Y.)

    2021  Volume 374, Issue 6571, Page(s) 1127–1133

    Abstract: Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear ...

    Abstract Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis
    MeSH term(s) Adult ; Black or African American/genetics ; Aged ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/physiopathology ; Disease Susceptibility ; Gene Expression Regulation ; Genetic Variation ; Humans ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza, Human/genetics ; Influenza, Human/immunology ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/virology ; Male ; Middle Aged ; Quantitative Trait Loci ; Severity of Illness Index ; Single-Cell Analysis ; Transcription, Genetic ; Viral Load ; White People/genetics ; Young Adult
    Chemical Substances Interferon Type I
    Language English
    Publishing date 2021-11-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abg0928
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  9. Article ; Online: Gene activation precedes DNA demethylation in response to infection in human dendritic cells.

    Pacis, Alain / Mailhot-Léonard, Florence / Tailleux, Ludovic / Randolph, Haley E / Yotova, Vania / Dumaine, Anne / Grenier, Jean-Christophe / Barreiro, Luis B

    Proceedings of the National Academy of Sciences of the United States of America

    2019  Volume 116, Issue 14, Page(s) 6938–6943

    Abstract: DNA methylation is considered to be a relatively stable epigenetic mark. However, a growing body of evidence indicates that DNA methylation levels can change rapidly; for example, in innate immune cells facing an infectious agent. Nevertheless, the ... ...

    Abstract DNA methylation is considered to be a relatively stable epigenetic mark. However, a growing body of evidence indicates that DNA methylation levels can change rapidly; for example, in innate immune cells facing an infectious agent. Nevertheless, the causal relationship between changes in DNA methylation and gene expression during infection remains to be elucidated. Here, we generated time-course data on DNA methylation, gene expression, and chromatin accessibility patterns during infection of human dendritic cells with
    MeSH term(s) CpG Islands/immunology ; DNA Demethylation ; Dendritic Cells/immunology ; Dendritic Cells/microbiology ; Dendritic Cells/pathology ; Female ; Gene Expression Regulation/immunology ; Humans ; Male ; Mycobacterium tuberculosis/immunology ; Tuberculosis/immunology ; Tuberculosis/pathology
    Language English
    Publishing date 2019-03-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1814700116
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  10. Article ; Online: Harmful cyanobacterial aerosolization dynamics in the airshed of a eutrophic estuary.

    Plaas, Haley E / Paerl, Ryan W / Baumann, Karsten / Karl, Colleen / Popendorf, Kimberly J / Barnard, Malcolm A / Chang, Naomi Y / Curtis, Nathaniel P / Huang, Hwa / Mathieson, Olivia L / Sanchez, Joel / Maizel, Daniela J / Bartenfelder, Amy N / Braddy, Jeremy S / Hall, Nathan S / Rossignol, Karen L / Sloup, Randolph / Paerl, Hans W

    The Science of the total environment

    2022  Volume 852, Page(s) 158383

    Abstract: In addition to obvious negative effects on water quality in eutrophic aquatic ecosystems, recent work suggests that cyanobacterial harmful algal blooms (CHABs) also impact air quality via emissions carrying cyanobacterial cells and cyanotoxins. However, ... ...

    Abstract In addition to obvious negative effects on water quality in eutrophic aquatic ecosystems, recent work suggests that cyanobacterial harmful algal blooms (CHABs) also impact air quality via emissions carrying cyanobacterial cells and cyanotoxins. However, the environmental controls on CHAB-derived aerosol and its potential public health impacts remain largely unknown. Accordingly, the aims of this study were to 1) investigate the occurrence of microcystins (MC) and putatively toxic cyanobacterial communities in particulate matter ≤ 2.5 μm in diameter (PM
    MeSH term(s) Microcystins/analysis ; Estuaries ; Lakes/microbiology ; Ecosystem ; Cyanobacteria ; Harmful Algal Bloom ; Particulate Matter/analysis
    Chemical Substances Microcystins ; Particulate Matter
    Language English
    Publishing date 2022-09-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2022.158383
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