[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Commensal–dendritic-cell interaction specifies a unique protective skin immune signature

Nature volume 520, pages 104–108 (2015)Cite this article

Subjects

Abstract

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 immunity1,2,3,4. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges5,6,7. 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.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Remodelling of skin immunity by commensal colonization.
Figure 2: Distinct commensal species impose specific immune signatures in the skin.
Figure 3: Distinct dendritic cell subsets cooperate to mediate host–commensal interaction in the skin.
Figure 4: Commensal-driven CD8+ T cell response is specific for S. epidermidis antigen.

Similar content being viewed by others

Accession codes

Primary accessions

Sequence Read Archive

Data deposits

454 sequencing data are deposited in the Sequence Read Archive under accession number SRP039428.

References

  1. Grice, E. A. & Segre, J. A. The skin microbiome. Nature Rev. Microbiol. 9, 244–253 (2011)

    Article  CAS  Google Scholar 

  2. Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012)

    Article  ADS  CAS  Google Scholar 

  3. Chehoud, C. et al. Complement modulates the cutaneous microbiome and inflammatory milieu. Proc. Natl Acad. Sci. USA 110, 15061–15066 (2013)

    Article  ADS  CAS  Google Scholar 

  4. Sanford, J. A. & Gallo, R. L. Functions of the skin microbiota in health and disease. Semin. Immunol. 25, 370–377 (2013)

    Article  CAS  Google Scholar 

  5. Grice, E. A. et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 1190–1192 (2009)

    Article  ADS  CAS  Google Scholar 

  6. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009)

    Article  ADS  CAS  Google Scholar 

  7. Kong, H. H. et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850–859 (2012)

    Article  CAS  Google Scholar 

  8. Belkaid, Y. et al. CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. J. Immunol. 168, 3992–4000 (2002)

    Article  CAS  Google Scholar 

  9. Mueller, S. N., Gebhardt, T., Carbone, F. R. & Heath, W. R. Memory T cell subsets, migration patterns, and tissue residence. Annu. Rev. Immunol. 31, 137–161 (2013)

    Article  CAS  Google Scholar 

  10. Murphy, K. M. Transcriptional control of dendritic cell development. Adv. Immunol. 120, 239–267 (2013)

    Article  CAS  Google Scholar 

  11. Mittal, A. et al. Non-invasive delivery of nanoparticles to hair follicles: a perspective for transcutaneous immunization. Vaccine 31, 3442–3451 (2013)

    Article  CAS  Google Scholar 

  12. Caux, C. et al. Regulation of dendritic cell recruitment by chemokines. Transplantation 73, S7–S11 (2002)

    Article  MathSciNet  CAS  Google Scholar 

  13. Tamoutounour, S. et al. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39, 925–938 (2013)

    Article  CAS  Google Scholar 

  14. Igyártó, B. Z. et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity 35, 260–272 (2011)

    Article  Google Scholar 

  15. Bedoui, S. et al. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nature Immunol. 10, 488–495 (2009)

    Article  CAS  Google Scholar 

  16. Hildner, K. et al. Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity. Science 322, 1097–1100 (2008)

    Article  ADS  CAS  Google Scholar 

  17. Merad, M., Sathe, P., Helft, J., Miller, J. & Mortha, A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol. 31, 563–604 (2013)

    Article  CAS  Google Scholar 

  18. Hashimoto, D. et al. Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. J. Exp. Med. 208, 1069–1082 (2011)

    Article  CAS  Google Scholar 

  19. Vander Lugt, B. et al. Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation. Nature Immunol. 15, 161–167 (2014)

    Article  CAS  Google Scholar 

  20. Clark, R. A. et al. The vast majority of CLA+ T cells are resident in normal skin. J. Immunol. 176, 4431–4439 (2006)

    Article  CAS  Google Scholar 

  21. Lehmann-Grube, F., Dralle, H., Utermohlen, O. & Lohler, J. MHC class I molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice. J. Immunol. 153, 595–603 (1994)

    CAS  PubMed  Google Scholar 

  22. Yang, Y. et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510, 152–156 (2014)

    Article  ADS  CAS  Google Scholar 

  23. Goto, Y. et al. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity 40, 594–607 (2014)

    Article  CAS  Google Scholar 

  24. Lécuyer, E. et al. Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses. Immunity 40, 608–620 (2014)

    Article  Google Scholar 

  25. Gebhardt, C., Nemeth, J., Angel, P. & Hess, J. S100A8 and S100A9 in inflammation and cancer. Biochem. Pharmacol. 72, 1622–1631 (2006)

    Article  CAS  Google Scholar 

  26. Mose, M., Kang, Z., Raaby, L., Iversen, L. & Johansen, C. TNFα- and IL-17A-mediated S100A8 expression is regulated by p38 MAPK. Exp. Dermatol. 22, 476–481 (2013)

    Article  CAS  Google Scholar 

  27. Nowak, J. A. & Fuchs, E. Isolation and culture of epithelial stem cells. Methods Mol. Biol. 482, 215–232 (2009)

    Article  CAS  Google Scholar 

  28. Oh, J., Conlan, S., Polley, E. C., Segre, J. A. & Kong, H. H. Shifts in human skin and nares microbiota of healthy children and adults. Genome med. 4, 77 (2012)

    Article  Google Scholar 

  29. Martin, D. A. et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J. Invest. Dermatol. 133, 17–26 (2013)

    Article  CAS  Google Scholar 

  30. Burnett, S. H. et al. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene. J. Leukoc. Biol. 75, 612–623 (2004)

    Article  CAS  Google Scholar 

  31. Grice, E. A. et al. Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response. Proc. Natl Acad. Sci. USA 107, 14799–14804 (2010)

    Article  ADS  CAS  Google Scholar 

  32. Conlan, S. et al. Staphylococcus epidermidis pan-genome sequence analysis reveals diversity of skin commensal and hospital infection-associated isolates. Genome Biol. 13, R64 (2012)

    Article  Google Scholar 

  33. Gozalo, A. S. et al. Spontaneous Staphylococcus xylosus infection in mice deficient in NADPH oxidase and comparison with other laboratory mouse strains. J. Am. Assoc. Lab. Anim. Sci. 49, 480–486 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Spencer, S. P. et al. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science 343, 432–437 (2014)

    Article  ADS  CAS  Google Scholar 

  35. Helft, J. & Merad, M. Isolation of cutaneous dendritic cells. Methods Mol. Biol. 595, 231–233 (2010)

    Article  Google Scholar 

  36. Lennon, N. J. et al. A scalable, fully automated process for construction of sequence-ready barcoded libraries for 454. Genome Biol. 11, R15 (2010)

    Article  Google Scholar 

  37. Geiss, G. K. et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nature Biotechnol. 26, 317–325 (2008)

    Article  CAS  Google Scholar 

  38. Rittig, M. G. et al. Coiling phagocytosis of trypanosomatids and fungal cells. Infect. Immun. 66, 4331–4339 (1998)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID) and by the Human Frontier Science Program (C.W.). We thank the NIAID animal facility staff, in particular A. Gozalo (isolation of S. xylosus); D. Trageser-Cesler and C. Acevedo (NIAID gnotobiotic facility); K. Holmes, C. Eigsti and E. Stregevsky (NIAID sorting facility); K. Frank and F. Stock (MALDI-TOF analysis); B. Malissen (Langerin–GFP reporter mice); H. C. Morse (Irf8−/− mice); D. Kaplan (Langerin-DTA mice); R. Bosselut (B2m−/− mice); S. B. Hopping (collection of human skin tissue samples); J. Oh, K. Loré, and the Brenchley laboratory (technical advice and reagents); and K. Beacht and L. Martins dos Santos for technical assistance. We also thank the Belkaid laboratory for critical reading of the manuscript.

Author information

Author notes

  1. Shruti Naik

    Present address: Present addresses: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10065, USA.,

  2. Shruti Naik and Nicolas Bouladoux: These authors contributed equally to this work.

Authors and Affiliations

  1. Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, 20892, Bethesda, USA

    Shruti Naik, Nicolas Bouladoux, Jonathan L. Linehan, Seong-Ji Han, Oliver J. Harrison, Christoph Wilhelm, Sarah Himmelfarb, Allyson L. Byrd, Jason M. Brenchley & Yasmine Belkaid

  2. Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA,

    Shruti Naik, Nicolas Bouladoux, Jonathan L. Linehan, Seong-Ji Han, Oliver J. Harrison, Christoph Wilhelm, Sarah Himmelfarb, Allyson L. Byrd & Yasmine Belkaid

  3. Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, 20892, Maryland, USA

    Sean Conlan, Allyson L. Byrd, Clayton Deming & Julia A. Segre

  4. Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, NIH Bethesda, 20892, Maryland, USA

    Mariam Quinones

  5. Immunopathogenesis Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH Bethesda, 20892, Maryland, USA

    Jason M. Brenchley

  6. Dermatology Branch, National Cancer Institute, NIH Bethesda, 20892, Maryland, USA

    Heidi H. Kong

  7. Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, 63110, Missouri, USA

    Roxanne Tussiwand & Kenneth M. Murphy

  8. Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA

    Miriam Merad

Authors
  1. Shruti Naik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolas Bouladoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan L. Linehan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seong-Ji Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Oliver J. Harrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christoph Wilhelm
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sean Conlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sarah Himmelfarb
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Allyson L. Byrd
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Clayton Deming
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mariam Quinones
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jason M. Brenchley
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Heidi H. Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Roxanne Tussiwand
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kenneth M. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Miriam Merad
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Julia A. Segre
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yasmine Belkaid
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.N., N.B., and Y.B. designed the studies. S.N. and N.B. performed the experiments and analysed the data. J.L.L. assisted with in vitro co-culture studies and S.-J.H. with innate cell analysis and imaging. O.J.H. and C.W. provided technical assistance. S.C. and C.D. provided technical advice and performed 454 pyrosequencing. S.C. and M.Q. analysed 454 pyrosequencing data. S.H. assisted in processing of human and non-human primate skin tissue samples. A.L.B. performed NanoString data analysis. J.M.B. and H.H.K. provided technical advice and skin tissue samples from non-human primates and human patients, respectively. R.T., K.M.M. and M.M. assisted with design of dendritic cell depletion strategies. J.A.S. helped to design sequencing studies and provided guidance on bacterial isolates. S.N., N.B. and Y.B. wrote the manuscript.

Corresponding author

Correspondence to Yasmine Belkaid.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Assessment of Foxp3+ regulatory T cells and cytokine production by effector T cells after S. epidermidis topical application and/or intradermal inoculation.

a, Frequencies and absolute numbers of skin regulatory (CD45+ TCRβ+ CD4+ Foxp3+) T cells in unassociated mice (Ctrl, n = 4) and mice associated with S. epidermidis (n = 4) at day 14 post first topical application. b, Absolute numbers of effector T cells producing IL-17A after PMA/ionomycin stimulation in the skin (ear pinnae and flank), the lung or the small intestine lamina propria (gut) at day 14 post topical association (Ctrl, n = 4–5; S. epi., n = 4–5). c, d, Enumeration of colony-forming units and absolute numbers of effector T cells producing IFN-γ or IL-17A (PMA/ionomycin) from the skin 2 weeks post application with different doses (107, 108 or 109 c.f.u. per ml) of S. epidermidis (n = 4 per group). e, Frequencies and absolute numbers of neutrophils and monocytes in the skin of mice 14 days after the first topical application or intradermal inoculation with S. epidermidis (n = 4 per group). f, Assessment of cytokine production (mean ± s.e.m., n = 3 per time point) by leukocytes from the ear skin tissue 24 and 48 h after topical association with S. epidermidis. Unassociated mice were used as controls. No significant amounts of IL-4, IL-5, IL-17A, IL-18, IL-21 or IL-22 could be detected at the time of analysis. g, IFN-γ and IL-17A production by skin effector T cells in mice 7 days after S. epidermidis topical application or intradermal inoculation. h, Frequencies of IFN-γ and IL-17A-producing effector T cells in the skin of mice 7 and 14 days after the first topical application or intradermal inoculation of S. epidermidis (n = 4–5 mice per group). All results shown are representative of 2–3 experiments with similar results. *P < 0.05; **P < 0.01; ***P < 0.001; NS, not statistically significant as calculated by Student’s t-test.

Extended Data Figure 2 Assessment of CD8+ T-cell responses in the skin of specific pathogen-free and germ-free mice after topical application with skin commensals.

a, Mice were left unassociated (Ctrl, n = 5) or topically associated with S. epidermidis human isolate (n = 5), S. xylosus (n = 3), S. epidermidis murine isolate (S.epi 42E03, n = 2), S. lentus (n = 2), R. nasimurium (n = 2), S. aureus (n = 5), C. pseudodiphtheriticum (n = 3) or P. acnes (n = 3). Quantification of colony-forming units from the ears after topical application is shown 2 weeks after first association. b, Frequencies and numbers of effector (CD45+ TCRβ+ CD4+ Foxp3−) T cells producing IFN-γ or IL-17A after PMA/ionomycin stimulation in the skin of mice from a at day 14 post first topical application. Bar graphs represent the mean value from two mice. c, Frequencies of skin CD4+ and CD8β+ effector T cells in mice from a at day 14 post first topical application. d, Absolute numbers of IFN-γ- and IL-17A-producing CD8β+ effector T cells in the skin of unassociated (Ctrl) mice or mice associated with different doses (107, 108 or 109 c.f.u. per ml) of S. epidermidis (n = 4 per group). e, Absolute numbers of skin CD8β+ effector T cells in unassociated (Ctrl, n = 3) mice or mice associated with 1 ml (n = 5) or 5 ml (n = 5) of a suspension (109 c.f.u. per ml) of S. epidermidis. f, Flow cytometric assessment of the frequencies of CD4+ and CD8β+ effector T cells and absolute numbers of CD8β+ effector T cells in SPF (n = 3 per group) and germ-free (GF, n = 4 per group) mice 2 weeks after S. epidermidis topical application. g, Absolute numbers of IFN-γ- and IL-17A-producing CD8β+ effector T cells in the skin of unassociated (Ctrl) or S. epidermidis-associated C57BL/6 and BALB/c mice at 14 days post first topical application (n = 5 per group). For d–g, all results shown are representative of 2–3 independent experiments with similar results. *P < 0.05; **P < 0.01; ***P < 0.001; NS, not statistically significant as calculated with Student’s t-test. h, Quantification of colony-forming units from the ears of adult mice born from S. epidermidis-associated (S. epi+, n = 3) or unassociated (Ctrl, n = 3) breeder pairs. Flow plots and bar graphs (mean ± s.e.m.) illustrate the frequencies of CD4+ and CD8β+ effector T cells and absolute numbers of CD8β+ effector T cells, respectively. n.d., not detected; **P < 0.01 as calculated with Student’s t-test.

Extended Data Figure 3 CD8+ T cells accumulate preferentially in the epidermidis after topical application of S. epidermidis.

a, Proportion of effector (CD45+ TCRβ+ Foxp3−) CD8β+ T cells in the epidermal and dermal compartments of the ear skin tissue 2 weeks after the first S. epidermidis topical application. b, Representative imaging volume projected along the x axis of ears from Langerin–GFP reporter mice at 14 days post first topical application with S. epidermidis. Scale bars, 30 μm. c, Numbers of CD3+ CD8β+ cells producing IFN-γ or IL-17A (after PMA/ionomycin stimulation) from normal nonhuman primate (NHP) skin (n = 8). d, Assessment of IL-17A production in the supernatant of CD8β+ T cells purified from the skin of mice topically associated with S. epidermidis and cultured overnight in presence of anti-CD3ε alone (Ctrl) or with IL-1α and IL-1β (+ IL-1). Bars represent the mean value ± s.e.m. (n = 3, **P < 0.01 as calculated with Student’s t-test). Results shown in a, c and d are representative of 2–3 experiments with similar results.

Extended Data Figure 4 Depletion strategies for the different subsets of skin dendritic cells.

a, Gating strategy for various dendritic cell subsets in the skin. Cells are first gated on live CD45+ CD11c+ MHCII+. Subsets of dendritic cells are then defined as follows: Langerhans cells (LC) are gated on CD11b+ CD207(Langerin)+ cells, CD103+ dendritic cells (CD103 DC) on CD11b− CD207+ cells and CD11b+ dermal dendritic cells (CD11b DC) on CD11b+ CD207− cells. b, Comparative assessment by flow cytometry of Langerhans cell, CD103 DC and CD11b DC in the ear skin of unassociated mice (control) and mice first topically associated with S. epidermidis 2 weeks earlier. c, Absolute numbers of Langerhans cell, CD103 DC and CD11b DC 2 weeks after the first topical application of S. epidermidis in wild-type (WT, n = 3), Langerin–DTA (Lan–DTA, n = 3), Batf3−/− (n = 3) or Irf8−/− (n = 3) mice and in mice treated with anti-CSF1R (n = 3) or isotype control (rat IgG, n = 3) antibodies. d, Absolute numbers of CD11chiMHCII+ CD8+ DEC205+ dendritic cells in the spleen and the skin draining lymph node (dLN) of wild-type (n = 5) and Batf3−/− (n = 6) mice. e, Phenotypic analysis of CD45+ MHCII+ CD11c+ cells by flow cytometry and absolute numbers of effector (CD45+ TCRβ+ Foxp3−) CD8β+ T cells and IL-17A- or IFN-γ-producing CD8β+ T cells in wild-type (n = 3) and Irf8−/− (n = 3) mice 2 weeks after the first topical application of S. epidermidis. f, Assessment of IL-1 production by leukocytes from the ear skin tissue of S. epidermidis-associated mice treated with anti-CSF1R (n = 4) or isotype control (rat IgG, n = 5) antibodies. g, Frequencies of total and IFN-γ- or IL-17A- producing CD8β+ effector T cells in S. epidermidis-associated Irf4 fl/fl × CD11ccre+ (n = 3) and littermate control (n = 3) mice. All data shown in this figure are representative of 2–3 experiments with similar results. *P < 0.05; **P < 0.01; ***P < 0.001; NS, not statistically significant as calculated with Student’s t-test.

Extended Data Figure 5 Commensal-driven CD4+ and CD8+ T-cell responses in the skin tissue and the skin draining lymph nodes are specific for commensal antigens.

a, Frequencies of IFN-γ- or IL-17A-producing CD8β+ T cells in overnight co-cultures of splenic dendritic cells (SpDC) and CD8β+ T cells purified from the skin draining lymph node (dLN) of mice first topically associated with S. epidermidis 2 weeks earlier. b, Frequencies of IFN-γ- and IL-17A-producing CD8β+ T cells in overnight co-cultures of SpDC and CD8β+ T cells purified from the skin of mice 14 days after the first S. epidermidis application. Dendritic cells were purified from either wild-type (WT) or Abb−/− B2m−/− mice. c, d, Frequencies of IFN-γ- and IL-17A-producing CD4+ T cells in overnight co-cultures of SpDC and CD8β+ T cells purified from the skin ear tissue or the skin dLN of mice 14 days after the first S. epidermidis application. For a, b and d, Ctrl, naive SpDC; S. epi, SpDC + heat-killed S. epidermidis; Abb/B2m S. epi, Abb−/− B2m−/− SpDC + heat-killed S. epidermidis. e, Frequencies of IFN-γ- and IL-17A-producing CD4+ T cells in overnight co-cultures of SpDC and CD8β+ T cells purified from the skin ear tissue or the skin dLN of mice 14 days after the first S. xylosus application. Ctrl, naive SpDC; S. xylo, SpDC + heat-killed S. xylosus; Abb/B2m S. xylo, Abb−/− B2m−/− SpDC + heat-killed S. xylosus. All data shown in a–d are representative of three independent experiments. Graph bars represent the mean ± standard deviation of triplicate cultures. **P < 0.01, ***P < 0.0001, ****P < 0.0001 as calculated with Student’s t-test. f, S100a8 and S100a9 gene expression in dorsal skin biopsies of mice associated with different doses (107, 108 or 109 c.f.u. per ml) of S. epidermidis 2 weeks after the first topical application (n = 4 per group). Data are expressed as fold increase over gene expression in unassociated control mice.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Naik, S., Bouladoux, N., Linehan, J. et al. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520, 104–108 (2015). https://doi.org/10.1038/nature14052

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature14052

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing