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  • 1
    Publication Date: 2014-12-30
    Description: The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667810/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naik, Shruti -- Bouladoux, Nicolas -- Linehan, Jonathan L -- Han, Seong-Ji -- Harrison, Oliver J -- Wilhelm, Christoph -- Conlan, Sean -- Himmelfarb, Sarah -- Byrd, Allyson L -- Deming, Clayton -- Quinones, Mariam -- Brenchley, Jason M -- Kong, Heidi H -- Tussiwand, Roxanne -- Murphy, Kenneth M -- Merad, Miriam -- Segre, Julia A -- Belkaid, Yasmine -- R01 CA173861/CA/NCI NIH HHS/ -- R01 CA190400/CA/NCI NIH HHS/ -- U01 AI095611/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2015 Apr 2;520(7545):104-8. doi: 10.1038/nature14052. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA. ; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA [3] Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA. ; 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Immunopathogenesis Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA. ; Dermatology Branch, National Cancer Institute, NIH Bethesda, Maryland 20892, USA. ; Howard Hughes Medical Institute, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Bacterial/immunology ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Dendritic Cells/cytology/*immunology ; Humans ; Immunity, Innate/immunology ; Interleukin-17/immunology ; Langerhans Cells/cytology/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Primates ; Skin/cytology/*immunology/*microbiology ; Staphylococcus epidermidis/immunology ; Symbiosis/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-10-04
    Description: The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal and viral communities, which showed not only site specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalogue, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes and strain tracking, and defines the dual influence of biogeography and individuality on microbial composition and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185404/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185404/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oh, Julia -- Byrd, Allyson L -- Deming, Clay -- Conlan, Sean -- NISC Comparative Sequencing Program -- Kong, Heidi H -- Segre, Julia A -- 1K99AR059222/AR/NIAMS NIH HHS/ -- 1UH2AR057504-01/AR/NIAMS NIH HHS/ -- 4UH3AR057504-02/AR/NIAMS NIH HHS/ -- ZIA BC010938-06/Intramural NIH HHS/ -- ZIA HG000180-13/Intramural NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):59-64. doi: 10.1038/nature13786.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA. ; 1] Dermatology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA [2]. ; 1] Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279917" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/genetics/isolation & purification ; Female ; Genome, Bacterial/genetics ; Genome, Fungal/genetics ; Genome, Viral/genetics ; Genomics ; Healthy Volunteers ; Humans ; Male ; *Metagenome/genetics ; Phylogeny ; Propionibacterium acnes/genetics/isolation & purification/virology ; Skin/*microbiology/*virology ; Staphylococcus epidermidis/genetics/isolation & purification/virology ; Symbiosis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Byrd, Allyson L -- Segre, Julia A -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):224-6. doi: 10.1126/science.aad6753.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. Department of Bioinformatics, Boston University, Boston, MA 02215, USA. ; Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. jsegre@nhgri.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816362" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/adverse effects ; Clostridium difficile/pathogenicity ; Communicable Diseases/chemically induced/*microbiology ; Cross Infection/chemically induced/microbiology ; Diarrhea/chemically induced/microbiology ; Disease Susceptibility/chemically induced/microbiology ; Enterocolitis, Pseudomembranous/chemically induced/microbiology ; *Host-Pathogen Interactions ; Humans ; Mice ; *Microbial Consortia ; Symbiosis/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-06-03
    Description: Studies of the human microbiome have revealed that both site specificity and individuality play a role in shaping the microbial communities of healthy individuals (1). Longitudinal studies have determined that bacterial strains remain stable over time (2, 3), suggesting that microbial signatures may distinguish individuals. In PNAS, Franzosa et al....
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2018
    Description: 〈p〉Barrier tissues are primary targets of environmental stressors and home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells. Here, we show that skin-resident commensal-specific T cells harbor a paradoxical program characterized by a type-17 program associated with a poised type-2 state. Thus, in the context of injury and exposure to inflammatory mediators such as IL-18, these cells rapidly release type-2 cytokines, thereby acquiring contextual functions. Notably, such acquisition of a type-2 effector program promotes tissue repair. Aberrant type-2 responses can also be unleashed in the context of local defects in immunoregulation. Thus, commensal-specific T cells co-opt tissue residency and cell-intrinsic flexibility as a means to promote both local immunity and tissue adaptation to injury.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Natural Sciences in General
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  • 6
    Publication Date: 2019
    Description: 〈p〉Barrier tissues are primary targets of environmental stressors and are home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells. We found that skin-resident commensal-specific T cells harbor a paradoxical program characterized by a type 17 program associated with a poised type 2 state. Thus, in the context of injury and exposure to inflammatory mediators such as interleukin-18, these cells rapidly release type 2 cytokines, thereby acquiring contextual functions. Such acquisition of a type 2 effector program promotes tissue repair. Aberrant type 2 responses can also be unleashed in the context of local defects in immunoregulation. Thus, commensal-specific T cells co-opt tissue residency and cell-intrinsic flexibility as a means to promote both local immunity and tissue adaptation to injury.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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